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Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway. 姜黄素通过调节 Nrf2/GPX4 信号通路诱导骨肉瘤细胞的铁蛋白沉着和凋亡
IF 3.2 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2024-01-03 DOI: 10.1177/15353702231220670
Chuanjian Yuan, Rong Fan, Kai Zhu, Yutong Wang, Wenpeng Xie, Yanchen Liang
{"title":"Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway.","authors":"Chuanjian Yuan, Rong Fan, Kai Zhu, Yutong Wang, Wenpeng Xie, Yanchen Liang","doi":"10.1177/15353702231220670","DOIUrl":"10.1177/15353702231220670","url":null,"abstract":"<p><p>Curcumin, an antitumor agent, has been shown to inhibit cell growth and metastasis in osteosarcoma. However, there is no evidence of curcumin and its regulation of cell ferroptosis and nuclear factor E2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathways in osteosarcoma. This study aimed to investigate the effects of curcumin on osteosarcoma both <i>in vitro</i> and <i>in vivo</i>. To explore the effects and mechanisms of curcumin on osteosarcoma, cells (MNNG/HOS and MG-63) and xenograft mice models were established. Cell viability, cell apoptosis rate, cycle distribution, cell migration, cell invasion, reactive oxygen species, malonaldehyde and glutathione abilities, and protein levels were detected by cell counting kit-8, flow cytometry, wound healing, transwell assay, respectively. Nrf2 and GPX4 expressions were detected using an immunofluorescence assay. Nrf2/GPX4-related protein levels were detected using western blotting. The results showed that curcumin effectively decreased cell viability and increased apoptosis rate. Meanwhile, curcumin inhibited tumor volume in the xenograft model, and Nrf2/GPX4-related protein levels were also altered. Interestingly, the effects of curcumin were reversed by liproxstatin-1 (an effective inhibitor of ferroptosis) and bardoxolone-methyl (an effective activator of Nrf2). Our results indicate that curcumin has therapeutic effects on osteosarcoma cells and a xenograft model by regulating the expression of the Nrf2/GPX4 signaling pathway.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2183-2197"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080466","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}
引用次数: 0
Decision rules for personalized statin treatment prescriptions over multi-objectives. 多目标个性化他汀类药物治疗处方的决策规则。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2024-01-27 DOI: 10.1177/15353702231220660
Pui Ying Yew, Yue Liang, Terrence J Adam, Julian Wolfson, Peter J Tonellato, Chih-Lin Chi
{"title":"Decision rules for personalized statin treatment prescriptions over multi-objectives.","authors":"Pui Ying Yew, Yue Liang, Terrence J Adam, Julian Wolfson, Peter J Tonellato, Chih-Lin Chi","doi":"10.1177/15353702231220660","DOIUrl":"10.1177/15353702231220660","url":null,"abstract":"<p><p>In our previous study, we demonstrated the feasibility of producing a proactive statin prescription strategy - a personalized statin treatment plan (PSTP) - using neural networks with big data. However, its non-transparency limited result interpretations and clinical usability. To improve the transparency of our previous approach with minimal compromise to the maximal statin treatment benefit-to-risk ratio, this study proposed a five-step pipeline approach called the decision rules for statin treatment (DRST). Steps 1-3 of our proposed pipeline improved our previous PSTP model in optimizing individual benefit-to-risk ratio; Step 4 used a decision tree model (DRST) to provide straightforward rules in the initial statin treatment plan; Step 5 aimed to evaluate the efficacy of these decision rules by conducting a clinical trial simulation. We included 107,739 de-identified patient data from Optum Labs Database Warehouse in this study. The final decision rules were compact and efficient, resulting from a decision tree with only a maximum depth of 3 and 11 nodes. The DRST identified three factors that are easily obtainable at the point of care: age, low-density lipoprotein cholesterol (LDL-C) level, and age-adjusted Charlson score. Moreover, it also identified six subpopulations that can benefit most from these decision rules. In our clinical trial simulations, DRST was found to improve statin benefit in LDL-C reduction by 4.15 percentage points (pp) and reduce risks of statin-associated symptoms (SAS) and statin discontinuation by 11.71 and 3.96 pp, respectively, when compared to the standard of care. Moreover, these DRST results were only less than 0.6 pp suboptimal to PSTP, demonstrating that building DRST that provide transparency with minimal compromise to the maximal benefit-to-risk ratio of statin treatments is feasible.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2526-2537"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569681","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}
引用次数: 0
2-Bromopalmitate inhibits malignant behaviors of HPSCC cells by hindering the membrane location of Ras protein. 2-溴棕榈酸酯通过阻碍 Ras 蛋白的膜定位来抑制 HPSCC 细胞的恶性行为。
IF 3.2 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2023-12-30 DOI: 10.1177/15353702231220671
Chen Wang, Zhao-Yang Cui, Hai-Yan Chang, Chang-Zhen Wu, Zhao-Yan Yu, Xiao-Ting Wang, Yi-Qing Liu, Chang-Le Li, Xiang-Ge Du, Jian-Feng Li
{"title":"2-Bromopalmitate inhibits malignant behaviors of HPSCC cells by hindering the membrane location of Ras protein.","authors":"Chen Wang, Zhao-Yang Cui, Hai-Yan Chang, Chang-Zhen Wu, Zhao-Yan Yu, Xiao-Ting Wang, Yi-Qing Liu, Chang-Le Li, Xiang-Ge Du, Jian-Feng Li","doi":"10.1177/15353702231220671","DOIUrl":"10.1177/15353702231220671","url":null,"abstract":"<p><p>Palmitoylation, which is mediated by protein acyltransferase (PAT) and performs important biological functions, is the only reversible lipid modification in organism. To study the effect of protein palmitoylation on hypopharyngeal squamous cell carcinoma (HPSCC), the expression levels of 23 PATs in tumor tissues of 8 HPSCC patients were determined, and high mRNA and protein levels of DHHC9 and DHHC15 were found. Subsequently, we investigated the effect of 2-bromopalmitate (2BP), a small-molecular inhibitor of protein palmitoylation, on the behavior of Fadu cells in vitro (50 μM) and in nude mouse xenograft models (50 μmol/kg), and found that 2BP suppressed the proliferation, invasion, and migration of Fadu cells without increasing cell apoptosis. Mechanistically, the effect of 2BP on the transduction of BMP, Wnt, Shh, and FGF signaling pathways was tested with qRT-PCR, and its drug target was explored with western blotting and acyl-biotinyl exchange assay. Our results showed that 2BP inhibited the transduction of the FGF/ERK signaling pathway. The palmitoylation level of Ras protein decreased after 2BP treatment, and its distribution in the cell membrane structure was reduced significantly. The findings of this work reveal that protein palmitoylation mediated by DHHC9 and DHHC15 may play important roles in the occurrence and development of HPSCC. 2BP is able to inhibit the malignant biological behaviors of HPSCC cells, possibly via hindering the palmitoylation and membrane location of Ras protein, which might, in turn, offer a low-toxicity anti-cancer drug for targeting the treatment of HPSCC.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2393-2407"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073779","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}
引用次数: 0
Retraction Notice. 撤稿通知。
IF 3.2 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2024-01-02 DOI: 10.1177/15353702231222796
{"title":"Retraction Notice.","authors":"","doi":"10.1177/15353702231222796","DOIUrl":"10.1177/15353702231222796","url":null,"abstract":"","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2494"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073800","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}
引用次数: 0
Deep learning diagnostic performance and visual insights in differentiating benign and malignant thyroid nodules on ultrasound images. 在超声图像上区分甲状腺结节良性和恶性的深度学习诊断性能和视觉洞察力。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2024-01-26 DOI: 10.1177/15353702231220664
Yujiang Liu, Ying Feng, Linxue Qian, Zhixiang Wang, Xiangdong Hu
{"title":"Deep learning diagnostic performance and visual insights in differentiating benign and malignant thyroid nodules on ultrasound images.","authors":"Yujiang Liu, Ying Feng, Linxue Qian, Zhixiang Wang, Xiangdong Hu","doi":"10.1177/15353702231220664","DOIUrl":"10.1177/15353702231220664","url":null,"abstract":"<p><p>This study aims to construct and evaluate a deep learning model, utilizing ultrasound images, to accurately differentiate benign and malignant thyroid nodules. The objective includes visualizing the model's process for interpretability and comparing its diagnostic precision with a cohort of 80 radiologists. We employed ResNet as the classification backbone for thyroid nodule prediction. The model was trained using 2096 ultrasound images of 655 distinct thyroid nodules. For performance evaluation, an independent test set comprising 100 cases of thyroid nodules was curated. In addition, to demonstrate the superiority of the artificial intelligence (AI) model over radiologists, a Turing test was conducted with 80 radiologists of varying clinical experience. This was meant to assess which group of radiologists' conclusions were in closer alignment with AI predictions. Furthermore, to highlight the interpretability of the AI model, gradient-weighted class activation mapping (Grad-CAM) was employed to visualize the model's areas of focus during its prediction process. In this cohort, AI diagnostics demonstrated a sensitivity of 81.67%, a specificity of 60%, and an overall diagnostic accuracy of 73%. In comparison, the panel of radiologists on average exhibited a diagnostic accuracy of 62.9%. The AI's diagnostic process was significantly faster than that of the radiologists. The generated heat-maps highlighted the model's focus on areas characterized by calcification, solid echo and higher echo intensity, suggesting these areas might be indicative of malignant thyroid nodules. Our study supports the notion that deep learning can be a valuable diagnostic tool with comparable accuracy to experienced senior radiologists in the diagnosis of malignant thyroid nodules. The interpretability of the AI model's process suggests that it could be clinically meaningful. Further studies are necessary to improve diagnostic accuracy and support auxiliary diagnoses in primary care settings.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2538-2546"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566934","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}
引用次数: 0
The discovery of subunit-selective GluN1/GluN2B NMDAR antagonist via pharmacophere-based virtual screening. 通过基于药球的虚拟筛选发现亚单位选择性 GluN1/GluN2B NMDAR 拮抗剂。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2024-01-29 DOI: 10.1177/15353702231220666
Jialing Tang, Ju Jin, Zhihong Huang, Faliang An, Caiguo Huang, Wenli Jiang
{"title":"The discovery of subunit-selective GluN1/GluN2B NMDAR antagonist via pharmacophere-based virtual screening.","authors":"Jialing Tang, Ju Jin, Zhihong Huang, Faliang An, Caiguo Huang, Wenli Jiang","doi":"10.1177/15353702231220666","DOIUrl":"10.1177/15353702231220666","url":null,"abstract":"<p><p>The incidence and mortality rates of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are gradually increasing worldwide. Numerous studies have demonstrated that N-methyl-D-aspartic acid receptor (NMDAR)-mediated excitotoxicity contributes to neurodegenerative diseases. Ifenprodil, a subtype-selective NMDAR antagonist, showed strong therapeutic potential. However, it suffers from low oral bioavailability and off-target side effects. In this study, natural compounds were identified for selective inhibition of GluN1/GluN2B NMDAR of human. We obtained a set of natural compounds (<i>n</i> = 81,366) from COCONUT, TIPdb, PAMDB, CMNPD, YMDB, and NPAtlas databases, and then virtually screened by an ifenprodil-structure-based pharmacophore model and molecular docking. The top 100 compounds were selected for binding affinity prediction via batch drug-target affinity (BatchDTA). Then, the top 50 compounds were analyzed by absorption, distribution, metabolism, excretion, toxicity (ADMET). Molecular dynamics involving molecular mechanics/position-Boltzmann surface area (MM-PBSA) calculation were performed to further screening. The top 15 compounds with strong binding affinity and ifenprodil, a proven GluN2B-selective NMDAR antagonist, were subjected to molecular dynamic simulations (100 ns), root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), H-bonds, solvent accessible surface area (SASA), principal component analysis (PCA), and binding free energy calculations. Based on these analyses, one possible lead compound carrying positive charges (CNP0099440) was identified, with great binding affinity and less off-target activity by contrast to ifenprodil. CNP0099440 has great potential to be a GluN1/GluN2B NMDAR antagonist candidate and can be further detected via <i>in vitro</i> and <i>in vivo</i> experiments.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2560-2577"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569734","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}
引用次数: 0
A robust class decomposition-based approach for detecting Alzheimer's progression. 一种基于类分解的检测阿尔茨海默病进展的鲁棒方法。
IF 3.2 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2023-12-07 DOI: 10.1177/15353702231211880
Maha M Alwuthaynani, Zahraa S Abdallah, Raul Santos-Rodriguez
{"title":"A robust class decomposition-based approach for detecting Alzheimer's progression.","authors":"Maha M Alwuthaynani, Zahraa S Abdallah, Raul Santos-Rodriguez","doi":"10.1177/15353702231211880","DOIUrl":"10.1177/15353702231211880","url":null,"abstract":"<p><p>Computer-aided diagnosis of Alzheimer's disease (AD) is a rapidly growing field with the possibility to be utilized in practice. Deep learning has received much attention in detecting AD from structural magnetic resonance imaging (sMRI). However, training a convolutional neural network from scratch is problematic because it requires a lot of annotated data and additional computational time. Transfer learning can offer a promising and practical solution by transferring information learned from other image recognition tasks to medical image classification. Another issue is the dataset distribution's irregularities. A common classification issue in datasets is a class imbalance, where the distribution of samples among the classes is biased. For example, a dataset may contain more instances of some classes than others. Class imbalance is challenging because most machine learning algorithms assume that each class should have an equal number of samples. Models consequently perform poorly in prediction. Class decomposition can address this problem by making learning a dataset's class boundaries easier. Motivated by these approaches, we propose a class decomposition transfer learning (CDTL) approach that employs VGG19, AlexNet, and an entropy-based technique to detect AD from sMRI. This study aims to assess the robustness of the CDTL approach in detecting the cognitive decline of AD using data from various ADNI cohorts to determine whether comparable classification accuracy for the two or more cohorts would be obtained. Furthermore, the proposed model achieved state-of-the-art performance in predicting mild cognitive impairment (MCI)-to-AD conversion with an accuracy of 91.45%.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2514-2525"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498171","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}
引用次数: 0
Everolimus-induced hyperpermeability of endothelial cells causes lung injury. 依维莫司诱导的内皮细胞高渗透性会导致肺损伤。
IF 3.2 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2023-12-29 DOI: 10.1177/15353702231220672
Xiaolin Chen, Jianhui Chen, Shuihong Liu, Xianfan Li
{"title":"Everolimus-induced hyperpermeability of endothelial cells causes lung injury.","authors":"Xiaolin Chen, Jianhui Chen, Shuihong Liu, Xianfan Li","doi":"10.1177/15353702231220672","DOIUrl":"10.1177/15353702231220672","url":null,"abstract":"<p><p>The mammalian target of rapamycin (mTOR) inhibitors, everolimus (but not dactolisib), is frequently associated with lung injury in clinical therapies. However, the underlying mechanisms remain unclear. Endothelial cell barrier dysfunction plays a major role in the pathogenesis of the lung injury. This study hypothesizes that everolimus increases pulmonary endothelial permeability, which leads to lung injury. We tested the effects of everolimus on human pulmonary microvascular endothelial cell (HPMEC) permeability and a mouse model of intraperitoneal injection of everolimus was established to investigate the effect of everolimus on pulmonary vascular permeability. Our data showed that everolimus increased human pulmonary microvascular endothelial cell (HPMEC) permeability which was associated with MLC phosphorylation and F-actin stress fiber formation. Furthermore, everolimus induced an increasing concentration of intracellular calcium Ca<sup>2+</sup> leakage in HPMECs and this was normalized with ryanodine pretreatment. In addition, ryanodine decreased everolimus-induced phosphorylation of PKCα and MLC, and barrier disruption in HPMECs. Consistent with <i>in vitro</i> data, everolimus treatment caused a visible lung-vascular barrier dysfunction, including an increase in protein in BALF and lung capillary-endothelial permeability, which was significantly attenuated by pretreatment with an inhibitor of PKCα, MLCK, and ryanodine. This study shows that everolimus induced pulmonary endothelial hyper-permeability, at least partly, in an MLC phosphorylation-mediated EC contraction which is influenced in a Ca<sup>2+</sup>-dependent manner and can lead to lung injury through mTOR-independent mechanisms.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2440-2448"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073782","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}
引用次数: 0
Paraoxonase 1 rs662 polymorphism, its related variables, and COVID-19 intensity: Considering gender and post-COVID complications. Paraoxonase 1 rs662 多态性、其相关变量和 COVID-19 强度:考虑性别和 COVID 后并发症。
IF 3.2 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2022-10-31 DOI: 10.1177/15353702221128563
Zohreh-Al-Sadat Ghoreshi, Mojtaba Abbasi-Jorjandi, Gholamreza Asadikaram, Mohsen Sharif-Zak, Fatemeh Seyedi, Mohammad Khaksari Haddad, Mohammadreza Zangouey
{"title":"Paraoxonase 1 rs662 polymorphism, its related variables, and COVID-19 intensity: Considering gender and post-COVID complications.","authors":"Zohreh-Al-Sadat Ghoreshi, Mojtaba Abbasi-Jorjandi, Gholamreza Asadikaram, Mohsen Sharif-Zak, Fatemeh Seyedi, Mohammad Khaksari Haddad, Mohammadreza Zangouey","doi":"10.1177/15353702221128563","DOIUrl":"10.1177/15353702221128563","url":null,"abstract":"<p><p>In this study, we aimed to investigate the effect of paraoxonase 1 (PON1) rs662 polymorphism, arylesterase (ARE) activity, and the serum lipid profile in patients with coronavirus disease 2019 (COVID-19) in different stages of the disease considering post-COVID outcomes. A total of 470 COVID-19 patients (235 female and 235 male patients) were recruited into the study, and based on the World Health Organization (WHO) criteria, the patients were divided into three groups: moderate, severe, and critical. PON1 rs662 polymorphism was determined by the Alw 1 enzyme followed by agarose gel electrophoresis. Moreover, serum levels of triglycerides (TG), cholesterol (Chol), high-density lipoprotein-cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c), as well as the level of the ARE activity of PON1 in the sera of patients were measured at the time of infection and one and three months after hospitalization. There was a significant relationship between the G allele and the severity of the disease. In addition, the probability of death in homozygous individuals (GG) was higher than in heterozygous patients (GA), and it was higher in heterozygous patients than in wild-type individuals (AA). There was also a significant relationship between the decrease in serum lipids and the intensity of COVID-19. On the contrary, at the onset of the disease, the HDL-c level and serum ARE activity were reduced compared to one and three months after COVID-19 infection. The findings of this study indicated the significant impact of PON1 rs662 polymorphism on ARE activity, lipid profiles, disease severity, and mortality in COVID-19 patients.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2351-2362"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40436566","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}
引用次数: 0
4-Octyl itaconate alleviates renal ischemia reperfusion injury by ameliorating endoplasmic reticulum stress via Nrf2 pathway. 伊它康酸 4-辛酯通过 Nrf2 途径改善内质网应激,从而减轻肾缺血再灌注损伤
IF 3.2 4区 医学
Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2023-12-29 DOI: 10.1177/15353702231214255
Xiang-Kun Li, Hong-Juan Yang, Shi-Han Du, Bing Zhang, Ling-Yu Li, Shao-Na Li, Cui-Cui Liu, Yang Ma, Jian-Bo Yu
{"title":"4-Octyl itaconate alleviates renal ischemia reperfusion injury by ameliorating endoplasmic reticulum stress via Nrf2 pathway.","authors":"Xiang-Kun Li, Hong-Juan Yang, Shi-Han Du, Bing Zhang, Ling-Yu Li, Shao-Na Li, Cui-Cui Liu, Yang Ma, Jian-Bo Yu","doi":"10.1177/15353702231214255","DOIUrl":"10.1177/15353702231214255","url":null,"abstract":"<p><p>Renal ischemia-reperfusion injury (IRI) is a common clinical complication of multiple severe diseases. Owing to its high mortality and the lack of effective treatment, renal IRI is still an intractable problem for clinicians. Itaconate, which is a metabolite of cis-aconitate, can exert anti-inflammatory and antioxidant roles in many diseases. As a derivative of itaconate with high cell membrane permeability, 4-octyl itaconate (4-OI) could provide a protective effect for various diseases. However, the role of 4-OI in renal IRI is still unclear. Herein, we examined whether 4-OI afforded kidney protection through attenuating endoplasmic reticulum stress (ERS) via nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. To observe the effects of 4-OI on alleviating renal pathologic injury, improving renal dysfunction, decreasing inflammatory cytokines, and reducing oxidative stress, we utilized C57BL/6J mice with bilateral renal pedicle clamped and HK-2 cells with hypoxia/reoxygenation (H/R) exposure in our study. In addition, through western blot assay, we found 4-OI ameliorated renal IRI-induced ERS, and activated Nrf2 pathway. Moreover, Nrf2-knockout (KO) mice and Nrf2 knockdown HK-2 cells were used to validate the role of Nrf2 signaling pathway in 4-OI-mediated alleviation of ERS caused by renal IRI. We demonstrated that 4-OI relieved renal injury and suppressed ERS in wild-type mice, while the therapeutic role was not shown in Nrf2-KO mice. Similarly, 4-OI could exert cytoprotective effect and inhibit ERS in HK-2 cells after H/R, but not in Nrf2 knockdown cells. Our <i>in vivo</i> and <i>in vitro</i> studies revealed that 4-OI protected renal IRI through attenuating ERS via Nrf2 pathway.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2408-2420"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073780","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}
引用次数: 0
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