Introduction: The study was designed to explore how cinobufagin (CB) regulates the development of non-small cell lung cancer (NSCLC) cells through lipid rafts.
Material and methods: The effects of CB at gradient concentrations (0, 0.5, 1 and 2 µM) on NSCLC cell viability, apoptosis, reactive oxygen species (ROS) level, phosphorylation of Akt, and apoptosis- and lipid raft-related protein expression were assessed by MTT assay, flow cytometry and Western blot. Cholesterol and sphingomyelin were labeled with BODIPY to evaluate the effect of CB (2 µM) on them. Sucrose density gradient centrifugation was used to extract lipid rafts. The effect of CB on the expression and distribution of caveolin-1 was determined by immunofluorescence, quantitative reverse transcription polymerase chain reaction and Western blot. After overexpression of caveolin-1, the above experiments were performed again to observe whether the regulatory effect of CB was reversed.
Results: CB inhibited NSCLC cell viability while promoting apoptosis and ROS level. CB redistributed the lipid content on the membrane surface and reduced the content of caveolin-1 in the cell membrane. In addition, CB repressed the activation of AKT. However, caveolin-1 overexpression reversed the effects of CB on apoptosis, AKT activation and lipid raft.
Conclusions: CB regulates the activity of Akt in lipid rafts by inhibiting caveolin-1 expression to promote NSCLC cell apoptosis.
{"title":"Cinobufagin disrupts the stability of lipid rafts by inhibiting the expression of caveolin-1 to promote non-small cell lung cancer cell apoptosis.","authors":"Zhongqing Xu, Jinwei Li, Shuyu Fang, Mingzhu Lian, Changxiao Zhang, Jiahuan Lu, Kai Sheng","doi":"10.5114/aoms/174578","DOIUrl":"https://doi.org/10.5114/aoms/174578","url":null,"abstract":"<p><strong>Introduction: </strong>The study was designed to explore how cinobufagin (CB) regulates the development of non-small cell lung cancer (NSCLC) cells through lipid rafts.</p><p><strong>Material and methods: </strong>The effects of CB at gradient concentrations (0, 0.5, 1 and 2 µM) on NSCLC cell viability, apoptosis, reactive oxygen species (ROS) level, phosphorylation of Akt, and apoptosis- and lipid raft-related protein expression were assessed by MTT assay, flow cytometry and Western blot. Cholesterol and sphingomyelin were labeled with BODIPY to evaluate the effect of CB (2 µM) on them. Sucrose density gradient centrifugation was used to extract lipid rafts. The effect of CB on the expression and distribution of caveolin-1 was determined by immunofluorescence, quantitative reverse transcription polymerase chain reaction and Western blot. After overexpression of caveolin-1, the above experiments were performed again to observe whether the regulatory effect of CB was reversed.</p><p><strong>Results: </strong>CB inhibited NSCLC cell viability while promoting apoptosis and ROS level. CB redistributed the lipid content on the membrane surface and reduced the content of caveolin-1 in the cell membrane. In addition, CB repressed the activation of AKT. However, caveolin-1 overexpression reversed the effects of CB on apoptosis, AKT activation and lipid raft.</p><p><strong>Conclusions: </strong>CB regulates the activity of Akt in lipid rafts by inhibiting caveolin-1 expression to promote NSCLC cell apoptosis.</p>","PeriodicalId":8278,"journal":{"name":"Archives of Medical Science","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28eCollection Date: 2024-01-01DOI: 10.5114/aoms/189971
Josefina Yoaly Sánchez-López, Luis Carlos Díaz-Herrera, Lourdes Del Carmen Rizo-de la Torre
Introduction: Atrophic gastritis and intestinal metaplasia are precursor lesions of gastric cancer. The aim of this study was to determine the usefulness of the biomarkers pepsinogen I(PgI), pepsinogen II (PgII), gastrin-17, and H. pylori antibodies in the identification of precursor lesions.
Methods: We studied 129 patients with gastric symptoms. The biomarker status was determined using GastroPanel by means of the ELISA-technique.
Results: Biomarkers detected atrophy in 14% of the subjects, and 49.6% had positive antibodies for H. pylori. A PgI/PgII ratio < 3 was an important risk biomarker for precursor lesions in our population (OR = 9.171, 95% CI: 1.723-48.799, p = 0.009); however, biomarkers showed low accuracy with histopathological study.
Conclusions: In the Western Mexican population, precursor lesions (AG, IM) are common in adults (45%) with dyspepsia but infrequent in children (8%). H. pylori infection was detected in 41.3% of adults and 16.0% of children. Of the studied biomarkers, a PgI/PgII ratio < 3 was an important risk factor for precursor lesions such as AG or IM in our population, with an OR of 9.171 (95% CI: 1.723-48.799, p = 0.009).
简介：萎缩性胃炎和肠化生是胃癌的前兆病变：萎缩性胃炎和肠化生是胃癌的前驱病变。本研究旨在确定胃蛋白酶原 I (PgI)、胃蛋白酶原 II (PgII)、胃泌素-17 和幽门螺杆菌抗体等生物标志物在识别前驱病变中的作用：我们对 129 名有胃部症状的患者进行了研究。方法：我们对 129 名有胃部症状的患者进行了研究，通过 ELISA 技术使用 GastroPanel 对生物标志物状态进行了测定：结果：14%的受试者通过生物标志物检测到胃萎缩，49.6%的受试者幽门螺杆菌抗体呈阳性。PgI/PgII比值小于3是我们人群中前驱病变的重要风险生物标志物（OR = 9.171，95% CI：1.723-48.799，p = 0.009）；然而，生物标志物与组织病理学研究的准确性较低：在墨西哥西部人群中，前驱病变（AG、IM）常见于患有消化不良的成年人（45%），但在儿童中并不常见（8%）。41.3%的成人和16.0%的儿童检测出幽门螺杆菌感染。在所研究的生物标志物中，PgI/PgII 比率小于 3 是我们人群中出现 AG 或 IM 等前驱病变的重要风险因素，OR 值为 9.171（95% CI：1.723-48.799，P = 0.009）。
{"title":"Pepsinogen I, pepsinogen II, gastrin-17, and <i>Helicobacter pylori</i> serological biomarkers in the diagnosis of precursor lesions of gastric cancer.","authors":"Josefina Yoaly Sánchez-López, Luis Carlos Díaz-Herrera, Lourdes Del Carmen Rizo-de la Torre","doi":"10.5114/aoms/189971","DOIUrl":"https://doi.org/10.5114/aoms/189971","url":null,"abstract":"<p><strong>Introduction: </strong>Atrophic gastritis and intestinal metaplasia are precursor lesions of gastric cancer. The aim of this study was to determine the usefulness of the biomarkers pepsinogen I(PgI), pepsinogen II (PgII), gastrin-17, and <i>H. pylori</i> antibodies in the identification of precursor lesions.</p><p><strong>Methods: </strong>We studied 129 patients with gastric symptoms. The biomarker status was determined using GastroPanel by means of the ELISA-technique.</p><p><strong>Results: </strong>Biomarkers detected atrophy in 14% of the subjects, and 49.6% had positive antibodies for <i>H. pylori</i>. A PgI/PgII ratio < 3 was an important risk biomarker for precursor lesions in our population (OR = 9.171, 95% CI: 1.723-48.799, <i>p</i> = 0.009); however, biomarkers showed low accuracy with histopathological study.</p><p><strong>Conclusions: </strong>In the Western Mexican population, precursor lesions (AG, IM) are common in adults (45%) with dyspepsia but infrequent in children (8%). <i>H. pylori</i> infection was detected in 41.3% of adults and 16.0% of children. Of the studied biomarkers, a PgI/PgII ratio < 3 was an important risk factor for precursor lesions such as AG or IM in our population, with an OR of 9.171 (95% CI: 1.723-48.799, <i>p</i> = 0.009).</p>","PeriodicalId":8278,"journal":{"name":"Archives of Medical Science","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica T. Li, Amanda MM. Duddy, Michelle Cardona, V. Pasupuleti, Adrián V. Hernández
In patients with breast cancer and lymphoma, anthracyclines are associated with early and late dose-related cardiotoxicity. We systematically evaluated efficacy and harms of the use of beta-blockers in breast cancer and lymphoma patients undergoing chemotherapy.We searched five engines, and pre-prints until October 10, 2022, for randomised controlled trials (RCTs) evaluating beta-blockers for anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. Primary outcomes were all-cause mortality, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic diameter (LVEDD, LVESD), peak E’ velocity, E/A ratio, E/e’ ratio, NT-pro BNP levels. Secondary outcome was heart rate. Inverse variance random effect meta-analyses were performed, and we used GRADE methods to assess quality of evidence (QoE).Twelve RCTs were selected (n=1,794), seven RCTs evaluated carvedilol. Mean ages were 39 to 52 years-old, 88.5% were women; 79.4% had breast cancer, and 11.5% lymphoma. The evidence was very uncertain about the effect of beta-blockers on all-cause mortality (RR 0.87, 95%CI 0.55 to 1.37, 12 RCTs, I2=0%, very low QoE), LVEF (MD 2.73%, 95%CI -0.45% to 5.92%, 12 RCTs, I2=93%, very low QoE), and heart rate (MD -9.14 bpm, 95%CI -15.02 to -3.26, two RCTs, I2=87%, very low QoE) vs. controls. Beta-blockers likely reduced NT-pro BNP levels slightly (MD -15.35 pg/mL, 95%CI -22.39 to -8.31, two RCTs, I2=0%, moderate QoE). There were no effects on other outcomes, all with very low QoE.Prophylactic use of beta-blockers for cardioprotection had little to no effect on all-cause mortality, LVEF or cardiac function outcomes in cancer patients undergoing anthracycline therapy.
{"title":"Efficacy and harms associated with beta-blockers for cardiotoxicity in cancer patients undergoing chemotherapy: a systematic review and meta-analysis.","authors":"Jessica T. Li, Amanda MM. Duddy, Michelle Cardona, V. Pasupuleti, Adrián V. Hernández","doi":"10.5114/aoms/189501","DOIUrl":"https://doi.org/10.5114/aoms/189501","url":null,"abstract":"In patients with breast cancer and lymphoma, anthracyclines are associated with early and late dose-related cardiotoxicity. We systematically evaluated efficacy and harms of the use of beta-blockers in breast cancer and lymphoma patients undergoing chemotherapy.We searched five engines, and pre-prints until October 10, 2022, for randomised controlled trials (RCTs) evaluating beta-blockers for anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. Primary outcomes were all-cause mortality, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic diameter (LVEDD, LVESD), peak E’ velocity, E/A ratio, E/e’ ratio, NT-pro BNP levels. Secondary outcome was heart rate. Inverse variance random effect meta-analyses were performed, and we used GRADE methods to assess quality of evidence (QoE).Twelve RCTs were selected (n=1,794), seven RCTs evaluated carvedilol. Mean ages were 39 to 52 years-old, 88.5% were women; 79.4% had breast cancer, and 11.5% lymphoma. The evidence was very uncertain about the effect of beta-blockers on all-cause mortality (RR 0.87, 95%CI 0.55 to 1.37, 12 RCTs, I2=0%, very low QoE), LVEF (MD 2.73%, 95%CI -0.45% to 5.92%, 12 RCTs, I2=93%, very low QoE), and heart rate (MD -9.14 bpm, 95%CI -15.02 to -3.26, two RCTs, I2=87%, very low QoE) vs. controls. Beta-blockers likely reduced NT-pro BNP levels slightly (MD -15.35 pg/mL, 95%CI -22.39 to -8.31, two RCTs, I2=0%, moderate QoE). There were no effects on other outcomes, all with very low QoE.Prophylactic use of beta-blockers for cardioprotection had little to no effect on all-cause mortality, LVEF or cardiac function outcomes in cancer patients undergoing anthracycline therapy.","PeriodicalId":8278,"journal":{"name":"Archives of Medical Science","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141345018","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}
Fanyu Fu, Bo Liu, Hao Gu, Long Chen, Xiaoying Chen, Hengli Ye, Jiangtao Xie
Neck pain is common among adolescents and young adults, affecting their health and well-being. However, research on its prevalence trends in this demographic is limited despite its global significance.Data from the Global Burden of Disease Study was used to analyze neck pain prevalence and trends among individuals aged 10 to 24 from 1990 to 2019. Temporal trends and regional differences were assessed using estimated annual percentage changes.Globally, the number of adolescents and young adults affected by neck pain increased from 11,594,119 cases in 1990 to 12,880,134 in 2019. Despite this increase, the prevalence rate stabilized, dropping from 74,850.57 per 100,000 individuals in 1990 to 69,178.4 per 100,000 in 2019, with an annual decrease of -0.28%. In 2019, prevalence rates for ages 10-14, 15-19, and 20-24 were 31,624.66, 69,189.45, and 109,351.52 per 100,000 individuals, respectively. The regions with the highest prevalence rates in 2019 were Western Europe, High-income North America, and Southeast Asia, with rates of 1938.57, 1930.2, and 1021.37 per 100,000 individuals, respectively. Nationally, the United Kingdom, Denmark, and Finland had the highest rates, reaching 2,487.30, 2,442.03, and 2,336.94 cases per 100,000 individuals, respectively. Notably, regions with higher Socio-Demographic Index (SDI) levels tended to have higher prevalence rates of neck pain among adolescents and young adults, with variations by region and age group.The study emphasizes the ongoing burden of neck pain among adolescents and young adults worldwide, emphasizing the necessity for targeted interventions to enhance public health outcomes in this group.
{"title":"Temporal Trends in Neck Pain Prevalence among Adolescents and Young Adults Aged 10-24 from 1990 to 2019","authors":"Fanyu Fu, Bo Liu, Hao Gu, Long Chen, Xiaoying Chen, Hengli Ye, Jiangtao Xie","doi":"10.5114/aoms/190029","DOIUrl":"https://doi.org/10.5114/aoms/190029","url":null,"abstract":"Neck pain is common among adolescents and young adults, affecting their health and well-being. However, research on its prevalence trends in this demographic is limited despite its global significance.Data from the Global Burden of Disease Study was used to analyze neck pain prevalence and trends among individuals aged 10 to 24 from 1990 to 2019. Temporal trends and regional differences were assessed using estimated annual percentage changes.Globally, the number of adolescents and young adults affected by neck pain increased from 11,594,119 cases in 1990 to 12,880,134 in 2019. Despite this increase, the prevalence rate stabilized, dropping from 74,850.57 per 100,000 individuals in 1990 to 69,178.4 per 100,000 in 2019, with an annual decrease of -0.28%. In 2019, prevalence rates for ages 10-14, 15-19, and 20-24 were 31,624.66, 69,189.45, and 109,351.52 per 100,000 individuals, respectively. The regions with the highest prevalence rates in 2019 were Western Europe, High-income North America, and Southeast Asia, with rates of 1938.57, 1930.2, and 1021.37 per 100,000 individuals, respectively. Nationally, the United Kingdom, Denmark, and Finland had the highest rates, reaching 2,487.30, 2,442.03, and 2,336.94 cases per 100,000 individuals, respectively. Notably, regions with higher Socio-Demographic Index (SDI) levels tended to have higher prevalence rates of neck pain among adolescents and young adults, with variations by region and age group.The study emphasizes the ongoing burden of neck pain among adolescents and young adults worldwide, emphasizing the necessity for targeted interventions to enhance public health outcomes in this group.","PeriodicalId":8278,"journal":{"name":"Archives of Medical Science","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141350176","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}
Alzheimer's disease (AD) is triggered by biological mechanisms such as neuroinflammation and oxidative stress. Endoplasmic reticulum (ER) stress can lead to the expression of molecular chaperones in the ER, which helps in restoring cellular homeostasis. Researchers have highlighted the role of ER stress in the progression of AD, suggesting that regulating it could be a potential treatment strategy for AD.We induced AD in mice by injecting amyloid beta-peptide 25-35 (Aβ25-35) bilaterally into the CA1 of the dorsal hippocampus. Some mice were administered celastrol intraperitoneally before the Aβ25-35 injection, while others received it after the injection. The mice underwent the Barnes maze cognitive test and Morris water maze test to assess learning and memory impairment. Levels of interleukin (IL)-1β, tumor necrosis factor alpha, and IL-10 were measured to evaluate inflammation, while total antioxidant capacity, catalase, Malondialdehyde, and superoxide dismutase levels were analyzed to estimate oxidative stress.Our study showed that pre-treatment with celastrol could prevent learning and memory decline in AD mice by reducing inflammation and oxidative stress. Celastrol also inhibited AD-induced inflammation and oxidative stress. Additionally, celastrol suppressed AD progression by targeting ER stress. These results suggest that celastrol treatment could be beneficial in addressing learning and memory deficits in AD, paving the way for potential neuroprotective treatments.Celastrol effectively improved learning and memory impairments in AD mice by targeting ER stress-induced inflammation and oxidative stress. This highlights the potential of celastrol as a therapeutic agent for AD.
阿尔茨海默病（AD）是由神经炎症和氧化应激等生物机制引发的。内质网（ER）应激可导致ER中分子伴侣的表达，从而有助于恢复细胞的平衡。研究人员强调了内质网应激在AD进展中的作用，认为调节内质网应激可能是AD的一种潜在治疗策略。我们通过向小鼠背侧海马CA1注射淀粉样β肽25-35（Aβ25-35）诱导AD。一些小鼠在注射 Aβ25-35 之前腹腔注射了塞拉司琼，而另一些小鼠则在注射后注射了塞拉司琼。小鼠接受了巴恩斯迷宫认知测试和莫里斯水迷宫测试，以评估学习和记忆障碍。我们的研究表明，通过减少炎症和氧化应激，使用塞拉斯托前处理可预防AD小鼠的学习和记忆衰退。我们的研究表明，使用西司他醇预处理可通过减少炎症和氧化应激预防AD小鼠的学习和记忆衰退。此外，塞拉司醇还能通过靶向ER应激抑制AD的进展。这些结果表明， Celastrol 治疗可能有益于解决 AD 的学习和记忆障碍，为潜在的神经保护治疗铺平了道路。Celastrol 通过靶向 ER 应激诱导的炎症和氧化应激，有效改善了 AD 小鼠的学习和记忆损伤，这凸显了 Celastrol 作为 AD 治疗剂的潜力。
{"title":"Celastrol attenuates Alzheimer's disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress","authors":"Fan‐fan Cao, Limin Xu, Xiaoxue He, Yongbin Chi, Ying Wang, Denghai Zhang, Qiuyun Liu","doi":"10.5114/aoms/189906","DOIUrl":"https://doi.org/10.5114/aoms/189906","url":null,"abstract":"Alzheimer's disease (AD) is triggered by biological mechanisms such as neuroinflammation and oxidative stress. Endoplasmic reticulum (ER) stress can lead to the expression of molecular chaperones in the ER, which helps in restoring cellular homeostasis. Researchers have highlighted the role of ER stress in the progression of AD, suggesting that regulating it could be a potential treatment strategy for AD.We induced AD in mice by injecting amyloid beta-peptide 25-35 (Aβ25-35) bilaterally into the CA1 of the dorsal hippocampus. Some mice were administered celastrol intraperitoneally before the Aβ25-35 injection, while others received it after the injection. The mice underwent the Barnes maze cognitive test and Morris water maze test to assess learning and memory impairment. Levels of interleukin (IL)-1β, tumor necrosis factor alpha, and IL-10 were measured to evaluate inflammation, while total antioxidant capacity, catalase, Malondialdehyde, and superoxide dismutase levels were analyzed to estimate oxidative stress.Our study showed that pre-treatment with celastrol could prevent learning and memory decline in AD mice by reducing inflammation and oxidative stress. Celastrol also inhibited AD-induced inflammation and oxidative stress. Additionally, celastrol suppressed AD progression by targeting ER stress. These results suggest that celastrol treatment could be beneficial in addressing learning and memory deficits in AD, paving the way for potential neuroprotective treatments.Celastrol effectively improved learning and memory impairments in AD mice by targeting ER stress-induced inflammation and oxidative stress. This highlights the potential of celastrol as a therapeutic agent for AD.","PeriodicalId":8278,"journal":{"name":"Archives of Medical Science","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141354840","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}
Bing Gao, Tiantian Gong, Zhuocao Qi, Lan Li, Pan Liu, Ran Xia, Lingji Li, Jing Wang
This study investigates the molecular mechanisms by which excessive autophagy exacerbates post-myocardial infarction heart failure(post-MI HF) through nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and ferroptosis.We developed a post-MI heart failure model in Sprague-Dawley rats via coronary artery ligation, alongside an in vitro heart failure model using hypoxia/reoxygenation-stimulated H9C2 cells. Intervention with rapamycin (autophagy activator), 3-methyladenine (autophagy inhibitor), desferrioxamine, and ferredoxin-1(ferroptosis inhibitors). Various techniques, including echocardiography, immunofluorescence colocalization, C11 BODIPY 581/591 staining, flow cytometry, transmission electron microscopy, western blotting, and RT-qPCR, were employed.In vivo analyses revealed that NCOA4-mediated ferritinophagy and ferroptosis are significant in post-MI HF. Manipulating autophagy through rapamycin and 3-methyladenine influenced the expression of NCOA4 and glutathione peroxidase 4 (GPX4), subsequently affecting ferroptosis and modulating heart failure severity. Our in vitro experiments corroborated these findings, demonstrating that heightened autophagy amplifies NCOA4 expression, which in turn fosters ferroptosis and exacerbates myocardial injury. Interestingly, silencing of NCOA4 partially mitigated autophagy-induced iron deficiency, indicating a crucial intersection between autophagy and iron metabolism. Moreover, the cardioprotective effects observed following NCOA4 silencing were negated by concurrent GPX4 silencing.Our findings elucidate that autophagy precedes NCOA4 in its regulatory pathway and directly influences ferritinophagy. Enhanced autophagy augments intracellular free iron and unstable iron pools, triggering lipid peroxidation through ferritinophagy, which promotes ferroptosis and impairs cardiac function. These insights offer a novel scientific basis for developing therapeutic strategies for heart failure post-MI HF.
{"title":"Excessive autophagy of myocardial cells promotes ferroptosis and exacerbates heart failure in the state of myocardial infarction","authors":"Bing Gao, Tiantian Gong, Zhuocao Qi, Lan Li, Pan Liu, Ran Xia, Lingji Li, Jing Wang","doi":"10.5114/aoms/188719","DOIUrl":"https://doi.org/10.5114/aoms/188719","url":null,"abstract":"This study investigates the molecular mechanisms by which excessive autophagy exacerbates post-myocardial infarction heart failure(post-MI HF) through nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and ferroptosis.We developed a post-MI heart failure model in Sprague-Dawley rats via coronary artery ligation, alongside an in vitro heart failure model using hypoxia/reoxygenation-stimulated H9C2 cells. Intervention with rapamycin (autophagy activator), 3-methyladenine (autophagy inhibitor), desferrioxamine, and ferredoxin-1(ferroptosis inhibitors). Various techniques, including echocardiography, immunofluorescence colocalization, C11 BODIPY 581/591 staining, flow cytometry, transmission electron microscopy, western blotting, and RT-qPCR, were employed.In vivo analyses revealed that NCOA4-mediated ferritinophagy and ferroptosis are significant in post-MI HF. Manipulating autophagy through rapamycin and 3-methyladenine influenced the expression of NCOA4 and glutathione peroxidase 4 (GPX4), subsequently affecting ferroptosis and modulating heart failure severity. Our in vitro experiments corroborated these findings, demonstrating that heightened autophagy amplifies NCOA4 expression, which in turn fosters ferroptosis and exacerbates myocardial injury. Interestingly, silencing of NCOA4 partially mitigated autophagy-induced iron deficiency, indicating a crucial intersection between autophagy and iron metabolism. Moreover, the cardioprotective effects observed following NCOA4 silencing were negated by concurrent GPX4 silencing.Our findings elucidate that autophagy precedes NCOA4 in its regulatory pathway and directly influences ferritinophagy. Enhanced autophagy augments intracellular free iron and unstable iron pools, triggering lipid peroxidation through ferritinophagy, which promotes ferroptosis and impairs cardiac function. These insights offer a novel scientific basis for developing therapeutic strategies for heart failure post-MI HF.","PeriodicalId":8278,"journal":{"name":"Archives of Medical Science","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141351152","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}
D. Pella, Tibor Poruban, Jozef Gonsorcik, Jan Fedacko, Zuzana Pella, Karolina Angela Sieradzka Uchnar, Radka Hreskova, Marianna Barbierik Vachalcova
The growing interest in Vitamin D deficiency as a potential contributor to coronary artery disease (CAD) has prompted increased scrutiny. Nevertheless, its status as a confirmed risk factor remains unestablished. This study seeks to explore the connection between serum vitamin D levels and CAD.Employing a cross-sectional approach, 205 patients eligible for coronary computed tomography angiography (CCTA) were chosen. Serum vitamin D levels were assessed and juxtaposed with the outcomes of CCTA, which encompassed the coronary artery calcium score (CACS), as well as the presence and severity of coronary artery involvement attributed to atherosclerotic plaques.The average age of the participants was 61.4±10.8 years, and the mean serum vitamin D level was 19.6±10.3 ng/dl (ranging from 4.7 to 39.7 ng/dl). In total, 52.1% of the participants (n=107) exhibited vitamin D deficiency, 35.1% (n=72) had insufficient levels, and 12.6% (n=26) had sufficient levels of vitamin D. The mean serum vitamin D level was notably lower in patients with severe coronary artery disease (CAD) (P<0.0001). According to the Spearman test, a significant negative correlation (-0.48) was identified between the serum vitamin D level and CACS (P<0.0001). Conversely, the mean CACS in the vitamin D deficient group was significantly higher than in the insufficient and sufficient vitamin D groups (P<0.0001 for both comparisons).There was a correlation between vitamin D deficiency and both CACS and the severity of coronary artery stenosis.
维生素 D 缺乏症是冠状动脉疾病（CAD）的潜在诱因之一，这一问题日益受到人们的关注。然而，维生素 D 作为一种确证风险因素的地位仍未确定。本研究试图探讨血清维生素 D 水平与冠状动脉疾病之间的联系。研究采用横断面方法，选择了 205 名符合冠状动脉计算机断层扫描（CCTA）条件的患者。该研究采用横断面方法，选择了205名符合冠状动脉计算机断层扫描（CCTA）条件的患者，对他们的血清维生素D水平进行了评估，并将其与CCTA的结果（包括冠状动脉钙化评分（CACS）以及动脉粥样硬化斑块导致的冠状动脉受累的存在和严重程度）并列。52.1%的参与者（107 人）表现出维生素 D 缺乏，35.1% 的参与者（72 人）维生素 D 水平不足，12.6% 的参与者（26 人）维生素 D 水平充足。严重冠状动脉疾病（CAD）患者的平均血清维生素 D 水平明显较低（P<0.0001）。根据斯皮尔曼检验，血清维生素 D 水平与 CACS 之间存在显著的负相关（-0.48）（P<0.0001）。相反，维生素 D 缺乏组的 CACS 平均值明显高于维生素 D 不足组和维生素 D 充足组（两组比较，P<0.0001）。
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Although several observational studies have explored the association between sleep traits and the risk of erectile dysfunction (ED), it remains controversial. In the present study, we included a wide range of sleep traits that are commonly observed in clinical practice. We investigated the causal relationship between these sleep traits and ED using univariate and multivariate Mendelian randomization (MR) methods.Instrumental variables (IVs) for eight sleep traits (insomnia, sleep duration, chronotype, and sleep apnea syndrome), five confounders (depression, body mass index, smoking initiation, alcohol consumption, and type 2 diabetes), and ED were derived from genome-wide association study (GWAS) data of individuals of European ancestry. The primary analysis technique used was the inverse-variance weighted (IVW) approach. Furthermore, several sensitivity analyses were conducted to evaluate heterogeneity, horizontal pleiotropy, and stability.MR analysis revealed that increased snoring, short sleep, and frequent insomnia, were associated with a higher risk of ED. Furthermore, we found evidence of a significant association between being a morning person and the risk of developing ED. This association persisted in multivariable MR analyses after adjusting for potential confounding factors. Sensitivity analysis suggested that the results were robust with no evidence of pleiotropy or heterogeneity.This study provides further evidence supporting the association between genetically predicted snoring, insomnia, and an increased risk of ED. Additionally, the study highlights the causal relationship of short sleep duration and chronotype with ED.
尽管已有多项观察性研究探讨了睡眠特征与勃起功能障碍（ED）风险之间的关系，但这一问题仍存在争议。在本研究中，我们纳入了临床实践中常见的各种睡眠特征。八种睡眠特征（失眠、睡眠持续时间、慢性型和睡眠呼吸暂停综合征）、五种混杂因素（抑郁、体重指数、开始吸烟、饮酒和 2 型糖尿病）和 ED 的工具变量（IVs）均来自欧洲血统个体的全基因组关联研究（GWAS）数据。采用的主要分析技术是逆方差加权（IVW）方法。此外，我们还进行了几项敏感性分析，以评估异质性、水平多向性和稳定性。MR 分析显示，打鼾、睡眠时间短和经常失眠与较高的 ED 风险相关。此外，我们还发现晨起习惯与罹患 ED 的风险之间存在显著关联。在调整了潜在的混杂因素后，这种关联在多变量 MR 分析中依然存在。敏感性分析表明，结果是稳健的，没有证据表明存在多义性或异质性。这项研究提供了进一步的证据，支持遗传预测的打鼾、失眠与 ED 风险增加之间的关联。此外，该研究还强调了睡眠时间短和慢性型与 ED 之间的因果关系。
{"title":"Causal relationship between sleep traits and erectile dysfunction: Evidence from Mendelian Randomization analysis","authors":"Leilei Zhu, Qingqiang Gao, Xiaojia Guo, Zeqiao Xu, Jian Zhang","doi":"10.5114/aoms/188718","DOIUrl":"https://doi.org/10.5114/aoms/188718","url":null,"abstract":"Although several observational studies have explored the association between sleep traits and the risk of erectile dysfunction (ED), it remains controversial. In the present study, we included a wide range of sleep traits that are commonly observed in clinical practice. We investigated the causal relationship between these sleep traits and ED using univariate and multivariate Mendelian randomization (MR) methods.Instrumental variables (IVs) for eight sleep traits (insomnia, sleep duration, chronotype, and sleep apnea syndrome), five confounders (depression, body mass index, smoking initiation, alcohol consumption, and type 2 diabetes), and ED were derived from genome-wide association study (GWAS) data of individuals of European ancestry. The primary analysis technique used was the inverse-variance weighted (IVW) approach. Furthermore, several sensitivity analyses were conducted to evaluate heterogeneity, horizontal pleiotropy, and stability.MR analysis revealed that increased snoring, short sleep, and frequent insomnia, were associated with a higher risk of ED. Furthermore, we found evidence of a significant association between being a morning person and the risk of developing ED. This association persisted in multivariable MR analyses after adjusting for potential confounding factors. Sensitivity analysis suggested that the results were robust with no evidence of pleiotropy or heterogeneity.This study provides further evidence supporting the association between genetically predicted snoring, insomnia, and an increased risk of ED. Additionally, the study highlights the causal relationship of short sleep duration and chronotype with ED.","PeriodicalId":8278,"journal":{"name":"Archives of Medical Science","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141351697","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}
Ke Cao, Ru Gong, Jiancun Wang, Cong Yu, Ping Zheng
Long noncoding RNAs (lncRNAs) mediate critical effects in central nervous system diseases; however, the exact role of lncRNAs in human traumatic brain injury (TBI) remains elusive. Considering the principles of primary prediction, targeted prevention, and personalized treatment medicine (PPPM), identifying specific novel biomarker associated with TBI and exploring the underlying mechanisms comprehensively are crucial steps towards achieving primary prediction, targeted prevention, and personalized treatment of TBI.In this study, we integrated single-cell RNA sequencing (sc-RNA-seq) data and microarray chipset data for TBI to identify a competing endogenous RNA axis.We detected 11 clusters based on the sc-RNA-seq data and identified Ifit1 as a marker gene co-expressed with ENST00000505646.1 (RP11-704M14.1). Additionally, the expression of IFIT1 and RP11-704M14.1 was found to decrease with the severity of TBI. RP11-704M14.1 promoted neuronal proliferation, and its knockdown prevented this effect. Furthermore, we found that RP11-704M14.1 functions as an miR-6756-5p sponge and increases the expression of its target gene ALOX15.Our results show that RP11-704M14.1 promotes neuronal proliferation by sponging miR-6756-5p and regulating ALOX15 expression in brain insults; accordingly, targeting this lncRNA presents a promising avenue for advancing the transition from reactive medicine to PPPM in managing traumatic brain injury, potentially leading to significant clinical benefits.
{"title":"Long noncoding RNA RP11-704M14.1 Acts as a Sponge of miR-6756-5p to promote neuronal proliferation by Regulating ALOX15 Expression","authors":"Ke Cao, Ru Gong, Jiancun Wang, Cong Yu, Ping Zheng","doi":"10.5114/aoms/188720","DOIUrl":"https://doi.org/10.5114/aoms/188720","url":null,"abstract":"Long noncoding RNAs (lncRNAs) mediate critical effects in central nervous system diseases; however, the exact role of lncRNAs in human traumatic brain injury (TBI) remains elusive. Considering the principles of primary prediction, targeted prevention, and personalized treatment medicine (PPPM), identifying specific novel biomarker associated with TBI and exploring the underlying mechanisms comprehensively are crucial steps towards achieving primary prediction, targeted prevention, and personalized treatment of TBI.In this study, we integrated single-cell RNA sequencing (sc-RNA-seq) data and microarray chipset data for TBI to identify a competing endogenous RNA axis.We detected 11 clusters based on the sc-RNA-seq data and identified Ifit1 as a marker gene co-expressed with ENST00000505646.1 (RP11-704M14.1). Additionally, the expression of IFIT1 and RP11-704M14.1 was found to decrease with the severity of TBI. RP11-704M14.1 promoted neuronal proliferation, and its knockdown prevented this effect. Furthermore, we found that RP11-704M14.1 functions as an miR-6756-5p sponge and increases the expression of its target gene ALOX15.Our results show that RP11-704M14.1 promotes neuronal proliferation by sponging miR-6756-5p and regulating ALOX15 expression in brain insults; accordingly, targeting this lncRNA presents a promising avenue for advancing the transition from reactive medicine to PPPM in managing traumatic brain injury, potentially leading to significant clinical benefits.","PeriodicalId":8278,"journal":{"name":"Archives of Medical Science","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141353554","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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