Pub Date : 2024-09-13DOI: 10.3389/fmolb.2024.1429372
Chao Song, Zhenkui Hu, Jinhui Zhang
BackgroundThe lymphocyte-to-C-reactive protein ratio (LCR) was a novel biomarker of inflammation that had been implicated in various diseases. Nevertheless, the role of LCR in the context of sepsis patients admitted to the Intensive Care Unit (ICU) had not been thoroughly elucidated. This study aimed to determine the significance of the LCR in predicting the prognosis of sepsis patients within ICU.MethodsA sample of sepsis patients requiring ICU care was selected from the Affiliated Hospital of Jiangsu University. These patients were then segmented into four quartiles based on their LCR levels. The primary endpoint of the study was 30-day mortality and the secondary endpoint was the occurrence of Acute Kidney Injury (AKI). Survival analysis, via the Kaplan-Meier method and log-rank test, was conducted to assess survival rates. Cox proportional hazards regression and logistic regression models were employed to investigate the association between LCR and clinical outcomes. Additional subgroup analyses were conducted to evaluate the influence of other confounding factors on the relationship between LCR and patient outcomes.ResultsA total of 1,123 patients were enrolled in this study, with a median age of 75 (65–84) years, and 707 (63.0%) of them were male. The 30-day mortality rate was 28.1%, while the incidence of AKI was 45.6%. A progressive decrease in LCR levels was found to be associated with an increased cumulative incidence of 30-day mortality (log-rank P < 0.001). Multivariable Cox proportional hazards analyses demonstrated that LCR was an independent predictor of 30-day mortality [per 1-unit increase in LCR: HR (95%CI): 0.370 (0.142–0.963); P = 0.042]. Additionally, multivariable logistic regression analysis revealed a significant association between LCR and AKI occurrence [per 1-unit increase in LCR: OR (95%CI): 0.541 (0.307–0.953); P = 0.034]. Furthermore, subgroup analysis indicated a stronger correlation for patients aged over 65 years compared to those aged 65 or younger (p for interaction <0.05) in predicting 30-day mortality or AKI occurrence based on LCR.ConclusionA reduction in LCR was notably linked to 30-day mortality and the occurrence of AKI in sepsis patients. These findings suggested that LCR could potentially serve as a valuable tool in identifying sepsis patients at a heightened risk of adverse outcomes.
{"title":"The value of lymphocyte-to-C-reactive protein ratio for predicting clinical outcomes in patients with sepsis in intensive care unit: a retrospective single-center study","authors":"Chao Song, Zhenkui Hu, Jinhui Zhang","doi":"10.3389/fmolb.2024.1429372","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1429372","url":null,"abstract":"BackgroundThe lymphocyte-to-C-reactive protein ratio (LCR) was a novel biomarker of inflammation that had been implicated in various diseases. Nevertheless, the role of LCR in the context of sepsis patients admitted to the Intensive Care Unit (ICU) had not been thoroughly elucidated. This study aimed to determine the significance of the LCR in predicting the prognosis of sepsis patients within ICU.MethodsA sample of sepsis patients requiring ICU care was selected from the Affiliated Hospital of Jiangsu University. These patients were then segmented into four quartiles based on their LCR levels. The primary endpoint of the study was 30-day mortality and the secondary endpoint was the occurrence of Acute Kidney Injury (AKI). Survival analysis, via the Kaplan-Meier method and log-rank test, was conducted to assess survival rates. Cox proportional hazards regression and logistic regression models were employed to investigate the association between LCR and clinical outcomes. Additional subgroup analyses were conducted to evaluate the influence of other confounding factors on the relationship between LCR and patient outcomes.ResultsA total of 1,123 patients were enrolled in this study, with a median age of 75 (65–84) years, and 707 (63.0%) of them were male. The 30-day mortality rate was 28.1%, while the incidence of AKI was 45.6%. A progressive decrease in LCR levels was found to be associated with an increased cumulative incidence of 30-day mortality (log-rank <jats:italic>P</jats:italic> &lt; 0.001). Multivariable Cox proportional hazards analyses demonstrated that LCR was an independent predictor of 30-day mortality [per 1-unit increase in LCR: HR (95%CI): 0.370 (0.142–0.963); <jats:italic>P</jats:italic> = 0.042]. Additionally, multivariable logistic regression analysis revealed a significant association between LCR and AKI occurrence [per 1-unit increase in LCR: OR (95%CI): 0.541 (0.307–0.953); <jats:italic>P</jats:italic> = 0.034]. Furthermore, subgroup analysis indicated a stronger correlation for patients aged over 65 years compared to those aged 65 or younger (<jats:italic>p</jats:italic> for interaction &lt;0.05) in predicting 30-day mortality or AKI occurrence based on LCR.ConclusionA reduction in LCR was notably linked to 30-day mortality and the occurrence of AKI in sepsis patients. These findings suggested that LCR could potentially serve as a valuable tool in identifying sepsis patients at a heightened risk of adverse outcomes.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IntroductionDiabetic macular edema (DME) is a major cause of vision loss in the sick with diabetic retinopathy. The occurrence of DME is closely related to the breakdown of neurovascular coupling; however, its underlying mechanism has not been fully elucidated. The aim of this study was to investigate the diagnostic biomarkers and potential molecular mechanisms associated with neurovascular coupling in DME.MethodsThe differential expression analysis, STEM, and WGCNA were performed from GSE160306 to identify hub genes. The gene expression was validated by RT-qPCR. The relevant mechanisms of action were investigated through GO, KEGG, and GSEA analyses, as well as co-expression networks. Additionally, the LASSO regression analysis and a nomogram were used to demonstrate the diagnostic effectiveness of the model. Finally, the GenDoma platform was utilized to identify drugs with potential therapeutic effects on DME.ResultsNeurotrophic factor receptor (NGFR) was identified as a hub gene related to neurovascular coupling and DME. The expression of NGFR was verified by RT-qPCR in vitro cells. GSEA analysis indicated that high expression of NGFR may affect immunity and inflammatory pathway, thereby regulating neurovascular coupling and mediating the development of DME. The NGFR co-expression network was constructed, which exhibited the correlation with the neurotrophin signaling pathway. Moreover, a diagnostic model for DME based on NGFR and PREX1 demonstrated relatively good diagnostic performance using LASSO regression analysis and the nomogram. And then the GenDoma platform identified drugs with potential therapeutic effects on DME.ConclusionThe high expression of NGFR may lead to abnormal neurovascular coupling and participate in the occurrence of DME by regulating the immunity, inflammatory and neurotrophin signaling pathway. Detection of NGFR and related expression genes may be beneficial for monitoring the occurrence and development of DME.
{"title":"Identification and mechanistic analysis of neurovascular coupling related biomarkers for diabetic macular edema","authors":"Tianpeng Chen, Shufan Sheng, Jing Chen, Xiaole Wang, Yanxing Shang, Chengwei Duan, Caixia Liang, Yu Song, Dongmei Zhang","doi":"10.3389/fmolb.2024.1332842","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1332842","url":null,"abstract":"IntroductionDiabetic macular edema (DME) is a major cause of vision loss in the sick with diabetic retinopathy. The occurrence of DME is closely related to the breakdown of neurovascular coupling; however, its underlying mechanism has not been fully elucidated. The aim of this study was to investigate the diagnostic biomarkers and potential molecular mechanisms associated with neurovascular coupling in DME.MethodsThe differential expression analysis, STEM, and WGCNA were performed from GSE160306 to identify hub genes. The gene expression was validated by RT-qPCR. The relevant mechanisms of action were investigated through GO, KEGG, and GSEA analyses, as well as co-expression networks. Additionally, the LASSO regression analysis and a nomogram were used to demonstrate the diagnostic effectiveness of the model. Finally, the GenDoma platform was utilized to identify drugs with potential therapeutic effects on DME.ResultsNeurotrophic factor receptor (NGFR) was identified as a hub gene related to neurovascular coupling and DME. The expression of NGFR was verified by RT-qPCR in <jats:italic>vitro</jats:italic> cells. GSEA analysis indicated that high expression of NGFR may affect immunity and inflammatory pathway, thereby regulating neurovascular coupling and mediating the development of DME. The NGFR co-expression network was constructed, which exhibited the correlation with the neurotrophin signaling pathway. Moreover, a diagnostic model for DME based on NGFR and PREX1 demonstrated relatively good diagnostic performance using LASSO regression analysis and the nomogram. And then the GenDoma platform identified drugs with potential therapeutic effects on DME.ConclusionThe high expression of NGFR may lead to abnormal neurovascular coupling and participate in the occurrence of DME by regulating the immunity, inflammatory and neurotrophin signaling pathway. Detection of NGFR and related expression genes may be beneficial for monitoring the occurrence and development of DME.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.3389/fmolb.2024.1458434
Huabin He, Yanhui Liao, Yang Chen, Hao Qin, Longlong Hu, Shucai Xiao, Huijian Wang, Renqiang Yang
BackgroundHypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by left ventricular hypertrophy that can lead to heart failure, arrhythmias, and sudden cardiac death. Despite extensive research, the molecular mechanisms underlying HCM are not fully understood, and effective treatments remain limited. By leveraging bioinformatics and experimental validation, this study aims to identify key genes and pathways involved in HCM, uncover novel drug candidates, and provide new insights into its pathogenesis and potential therapeutic strategies.MethodsCommonly upregulated and downregulated genes in hypertrophic cardiomyopathy (HCM) were identified using Gene Expression Omnibus (GEO) datasets, including three mRNA profiling datasets and one miRNA expression dataset. Enrichment analysis and hub-gene exploration were performed using interaction networks and consistent miRNA-mRNA matches. Potential drugs for HCM were screened. HCM cellular and animal models were established using isoproterenol. Key unstudied differentially expressed genes (DEGs) were validated. Animals were treated with novel potential drugs, and improvements in HCM were assessed via ultrasound metrics. Hematoxylin and eosin (H&E) staining was used to assess myocardial fibrosis. Immunohistochemistry was employed to detect DEGs in cellular experiments.ResultWe discovered 145 key upregulated and 149 downregulated DEGs associated with HCM development, among which there are eight core upregulated and seven core downregulated genes. There are 30 upregulated and six downregulated miRNAs. Between the six downregulated miRNAs and 1291 matched miRNAs (against eight core upregulated DEGs), there is one common miRNA, miR-1469. Using the CTD database, drugs that impact the expression/abundance/methylation/metabolic process of core DEGs (after the exclusion of toxic drugs) included acetaminophen, propylthiouracil, methapyrilene, triptolide, tretinoin, etc. In the HCM cell model, only ATRNL1 and WNT9A were significantly increased. In the HCM animal model, propylthiouracil, miR-1469, and triptolide demonstrated varying degrees of therapeutic effects on HCM. Propylthiouracil, but not miR-1469 or triptolide, significantly inhibited the expression of ATRNL1 in the HCM model, and all three drugs suppressed WNT9A expression.ConclusionWe identified several novel genes in HCM development, among which ATRNL1 and WNT9A were validated by cell and animal models. A deficiency of hsa-miR-1469 may be a mechanism behind HCM development. Novel medications for HCM treatment include propylthiouracil and triptolide.
{"title":"Identification of ATRNL1 and WNT9A as novel key genes and drug candidates in hypertrophic cardiomyopathy: integrative bioinformatics and experimental validation","authors":"Huabin He, Yanhui Liao, Yang Chen, Hao Qin, Longlong Hu, Shucai Xiao, Huijian Wang, Renqiang Yang","doi":"10.3389/fmolb.2024.1458434","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1458434","url":null,"abstract":"BackgroundHypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by left ventricular hypertrophy that can lead to heart failure, arrhythmias, and sudden cardiac death. Despite extensive research, the molecular mechanisms underlying HCM are not fully understood, and effective treatments remain limited. By leveraging bioinformatics and experimental validation, this study aims to identify key genes and pathways involved in HCM, uncover novel drug candidates, and provide new insights into its pathogenesis and potential therapeutic strategies.MethodsCommonly upregulated and downregulated genes in hypertrophic cardiomyopathy (HCM) were identified using Gene Expression Omnibus (GEO) datasets, including three mRNA profiling datasets and one miRNA expression dataset. Enrichment analysis and hub-gene exploration were performed using interaction networks and consistent miRNA-mRNA matches. Potential drugs for HCM were screened. HCM cellular and animal models were established using isoproterenol. Key unstudied differentially expressed genes (DEGs) were validated. Animals were treated with novel potential drugs, and improvements in HCM were assessed via ultrasound metrics. Hematoxylin and eosin (H&amp;E) staining was used to assess myocardial fibrosis. Immunohistochemistry was employed to detect DEGs in cellular experiments.ResultWe discovered 145 key upregulated and 149 downregulated DEGs associated with HCM development, among which there are eight core upregulated and seven core downregulated genes. There are 30 upregulated and six downregulated miRNAs. Between the six downregulated miRNAs and 1291 matched miRNAs (against eight core upregulated DEGs), there is one common miRNA, miR-1469. Using the CTD database, drugs that impact the expression/abundance/methylation/metabolic process of core DEGs (after the exclusion of toxic drugs) included acetaminophen, propylthiouracil, methapyrilene, triptolide, tretinoin, etc. In the HCM cell model, only <jats:italic>ATRNL1</jats:italic> and <jats:italic>WNT9A</jats:italic> were significantly increased. In the HCM animal model, propylthiouracil, miR-1469, and triptolide demonstrated varying degrees of therapeutic effects on HCM. Propylthiouracil, but not miR-1469 or triptolide, significantly inhibited the expression of <jats:italic>ATRNL1</jats:italic> in the HCM model, and all three drugs suppressed <jats:italic>WNT9A</jats:italic> expression.ConclusionWe identified several novel genes in HCM development, among which <jats:italic>ATRNL1</jats:italic> and <jats:italic>WNT9A</jats:italic> were validated by cell and animal models. A deficiency of hsa-miR-1469 may be a mechanism behind HCM development. Novel medications for HCM treatment include propylthiouracil and triptolide.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial: Lessons from external quality control in laboratory medicine: important implications for public health!","authors":"Nathalie Weiss, Ingo Schellenberg, Klaus-Peter Hunfeld","doi":"10.3389/fmolb.2024.1485193","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1485193","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ferroptosis, an iron-ion-dependent process of lipid peroxidation, damages the plasma membrane, leading to non-programmed cell death. Osteoarthritis (OA), a prevalent chronic degenerative joint disease among middle-aged and older adults, is characterized by chondrocyte damage or loss. Emerging evidence indicates that chondrocyte ferroptosis plays a role in OA development. However, most research has concentrated on ferroptosis regulation involving typical iron ions, potentially neglecting the significance of elevated copper ions in both serum and joint fluid of patients with OA. This review aims to fill this gap by systematically examining the interplay between copper metabolism, oxidative stress, ferroptosis, and copper-associated cell death in OA. It will provide a comprehensive overview of copper ions’ role in regulating ferroptosis and their dual role in OA. This approach seeks to offer new insights for further research, prevention, and treatment of OA.
铁变态反应是一种依赖铁离子的脂质过氧化过程，会破坏质膜，导致细胞非程序性死亡。骨关节炎（OA）是中老年人中普遍存在的一种慢性退行性关节疾病，其特点是软骨细胞受损或丧失。新近的证据表明，软骨细胞铁蛋白沉积在 OA 的发展过程中起着一定的作用。然而，大多数研究都集中于涉及典型铁离子的铁变态反应调节，可能忽视了 OA 患者血清和关节液中铜离子升高的重要性。本综述旨在通过系统研究 OA 中铜代谢、氧化应激、铁变态反应和铜相关细胞死亡之间的相互作用来填补这一空白。它将全面概述铜离子在调节铁变态反应中的作用及其在 OA 中的双重作用。这种方法旨在为进一步研究、预防和治疗 OA 提供新的见解。
{"title":"Copper metabolism in osteoarthritis and its relation to oxidative stress and ferroptosis in chondrocytes","authors":"Qingyuan Yu, Yanan Xiao, Mengqi Guan, Xianshuai Zhang, Jianan Yu, Mingze Han, Zhenhua Li","doi":"10.3389/fmolb.2024.1472492","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1472492","url":null,"abstract":"Ferroptosis, an iron-ion-dependent process of lipid peroxidation, damages the plasma membrane, leading to non-programmed cell death. Osteoarthritis (OA), a prevalent chronic degenerative joint disease among middle-aged and older adults, is characterized by chondrocyte damage or loss. Emerging evidence indicates that chondrocyte ferroptosis plays a role in OA development. However, most research has concentrated on ferroptosis regulation involving typical iron ions, potentially neglecting the significance of elevated copper ions in both serum and joint fluid of patients with OA. This review aims to fill this gap by systematically examining the interplay between copper metabolism, oxidative stress, ferroptosis, and copper-associated cell death in OA. It will provide a comprehensive overview of copper ions’ role in regulating ferroptosis and their dual role in OA. This approach seeks to offer new insights for further research, prevention, and treatment of OA.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.3389/fmolb.2024.1458675
Afshan Masood, Hicham Benabdelkamel, Salini Scaria Joy, Abdulaziz Alhossan, Bashayr Alsuwayni, Ghalia Abdeen, Madhawi Aldhwayan, Nora A. Alfadda, Alexander Dimitri Miras, Assim A. Alfadda
IntroductionTreatment and management of obesity is clinically challenging. The inclusion of GLP-1 receptor agonists (GLP1RA) in the medical management of obesity has proven to be efficacious. However, mechanisms underlying the molecular changes arising from GLP1RA treatment in patients with obesity remain to be elucidated.MethodsA single-center, prospective study was undertaken to evaluate the changes in the plasma proteins after liraglutide 3 mg therapy in twenty patients (M/F: 7/13) with obesity (mean BMI 40.65 ± 3.7 kg/m2). Anthropometric and laboratory parameters were measured, and blood samples were collected at two time points: baseline, before initiating treatment (pretreatment group, PT), and after three months of receiving the full dose liraglutide 3 mg (posttreatment group, PoT). An untargeted label-free LC MSMS mass spectrometric approach combined with bioinformatics and network pathway analysis was used to determine changes in the proteomic profiles.ResultsThe mean age of the study participants was 36.0 ± 11.1 years. A statistically significant change was observed in weight, BMI and HbA1c levels between the PT and PoT groups (paired t-test, P < 0.001). A significant dysregulation was noted in the abundances of 151 proteins (31 up and 120 downregulated) between the two groups. The potential biomarkers were evaluated using receiver operating characteristic (ROC) curves. The top ten proteins (area under the curve (AUC) of 0.999 (95% CI)) were identified as potential biomarkers between PT and PoT groups and included Cystatin-B, major vault protein, and plastin-3, which were upregulated, whereas multimerin-2, large ribosomal P2, and proline–rich acidic protein 1 were downregulated in the PoT group compared with the PT group. The top network pathway identified using ingenuity pathway analysis (IPA), centered around dysregulation of MAPK, AKT, and PKc signaling pathways and related to cell-to-cell signaling and interaction, cellular assembly and organization, cellular compromise and a score of 46 with 25 focus proteins.DiscussionThrough label-free quantitative proteomic analysis, our study revealed significant dysregulation of plasma proteins after liraglutide 3 mg treatment in patients with obesity. The alterations in the proteomic profile between the PT and PoT groups demonstrated a decrease in levels of proteins involved in inflammation and oxidative stress pathways. On the other hand proteins involved in the glycolytic and lipolytic metabolic pathways as well as those participating in cytoskeletal and endothelial reorganization were observed to be increased. Understanding actions of liraglutide at a molecular and proteomic levels provides a holistic look into how liraglutide impacts metabolism, induces weight loss and improves overall metabolic health.
{"title":"Label-free quantitative proteomic profiling reveals differential plasma protein expression in patients with obesity after treatment with liraglutide","authors":"Afshan Masood, Hicham Benabdelkamel, Salini Scaria Joy, Abdulaziz Alhossan, Bashayr Alsuwayni, Ghalia Abdeen, Madhawi Aldhwayan, Nora A. Alfadda, Alexander Dimitri Miras, Assim A. Alfadda","doi":"10.3389/fmolb.2024.1458675","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1458675","url":null,"abstract":"IntroductionTreatment and management of obesity is clinically challenging. The inclusion of GLP-1 receptor agonists (GLP1RA) in the medical management of obesity has proven to be efficacious. However, mechanisms underlying the molecular changes arising from GLP1RA treatment in patients with obesity remain to be elucidated.MethodsA single-center, prospective study was undertaken to evaluate the changes in the plasma proteins after liraglutide 3 mg therapy in twenty patients (M/F: 7/13) with obesity (mean BMI 40.65 ± 3.7 kg/m<jats:sup>2</jats:sup>). Anthropometric and laboratory parameters were measured, and blood samples were collected at two time points: baseline, before initiating treatment (pretreatment group, PT), and after three months of receiving the full dose liraglutide 3 mg (posttreatment group, PoT). An untargeted label-free LC MSMS mass spectrometric approach combined with bioinformatics and network pathway analysis was used to determine changes in the proteomic profiles.ResultsThe mean age of the study participants was 36.0 ± 11.1 years. A statistically significant change was observed in weight, BMI and HbA1c levels between the PT and PoT groups (paired t-test, <jats:italic>P</jats:italic> &lt; 0.001). A significant dysregulation was noted in the abundances of 151 proteins (31 up and 120 downregulated) between the two groups. The potential biomarkers were evaluated using receiver operating characteristic (ROC) curves. The top ten proteins (area under the curve (AUC) of 0.999 (95% CI)) were identified as potential biomarkers between PT and PoT groups and included Cystatin-B, major vault protein, and plastin-3, which were upregulated, whereas multimerin-2, large ribosomal P2, and proline–rich acidic protein 1 were downregulated in the PoT group compared with the PT group. The top network pathway identified using ingenuity pathway analysis (IPA), centered around dysregulation of MAPK, AKT, and PKc signaling pathways and related to cell-to-cell signaling and interaction, cellular assembly and organization, cellular compromise and a score of 46 with 25 focus proteins.DiscussionThrough label-free quantitative proteomic analysis, our study revealed significant dysregulation of plasma proteins after liraglutide 3 mg treatment in patients with obesity. The alterations in the proteomic profile between the PT and PoT groups demonstrated a decrease in levels of proteins involved in inflammation and oxidative stress pathways. On the other hand proteins involved in the glycolytic and lipolytic metabolic pathways as well as those participating in cytoskeletal and endothelial reorganization were observed to be increased. Understanding actions of liraglutide at a molecular and proteomic levels provides a holistic look into how liraglutide impacts metabolism, induces weight loss and improves overall metabolic health.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11eCollection Date: 2024-01-01DOI: 10.3389/fmolb.2024.1491755
[This retracts the article DOI: 10.3389/fmolb.2022.860525.].
[此文撤稿，DOI: 10.3389/fmolb.2022.860525.]。
{"title":"Retraction: Identification of a novel ferroptosis inducer for gastric cancer treatment using drug repurposing strategy.","authors":"","doi":"10.3389/fmolb.2024.1491755","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1491755","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3389/fmolb.2022.860525.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.3389/fmolb.2024.1348091
Hansotto Reiber
Cerebrospinal fluid (CSF) diagnostics is characterized by the biologically relevant combination of analytes in order to obtain disease-related data patterns that enable medically relevant interpretations. The necessary change in knowledge bases such as barrier function as a diffusion/CSF flow model and immunological networks of B-cell clones and pleiotropic cytokines is considered. The biophysical and biological principles for data combination are demonstrated using examples from neuroimmunological and dementia diagnostics. In contrast to current developments in clinical chemistry and laboratory medicine, CSF diagnostics is moving away from mega-automated systems with a constantly growing number of individual analyses toward a CSF report that integrates all patient data. Medical training in data sample interpretation in the inter-laboratory test systems (“EQA schemes”) has become increasingly important. However, the results for CSF diagnostics (EQAS from INSTAND) indicate a crucially misguided trend. The separate analysis of CSF and serum in different, non-matched assays and extreme batch variations systematically lead to misinterpretations, which are the responsibility of the test providers. The questionable role of expensive accreditation procedures and the associated false quality expectations are discussed. New concepts that reintegrate the medical expertise of the clinical chemist must be emphasized along with the positive side effect of reducing costs in the healthcare system.
{"title":"Disease-related data patterns in cerebrospinal fluid diagnostics: medical quality versus analytical quantity","authors":"Hansotto Reiber","doi":"10.3389/fmolb.2024.1348091","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1348091","url":null,"abstract":"Cerebrospinal fluid (CSF) diagnostics is characterized by the biologically relevant combination of analytes in order to obtain disease-related data patterns that enable medically relevant interpretations. The necessary change in knowledge bases such as barrier function as a diffusion/CSF flow model and immunological networks of B-cell clones and pleiotropic cytokines is considered. The biophysical and biological principles for data combination are demonstrated using examples from neuroimmunological and dementia diagnostics. In contrast to current developments in clinical chemistry and laboratory medicine, CSF diagnostics is moving away from mega-automated systems with a constantly growing number of individual analyses toward a CSF report that integrates all patient data. Medical training in data sample interpretation in the inter-laboratory test systems (“EQA schemes”) has become increasingly important. However, the results for CSF diagnostics (EQAS from INSTAND) indicate a crucially misguided trend. The separate analysis of CSF and serum in different, non-matched assays and extreme batch variations systematically lead to misinterpretations, which are the responsibility of the test providers. The questionable role of expensive accreditation procedures and the associated false quality expectations are discussed. New concepts that reintegrate the medical expertise of the clinical chemist must be emphasized along with the positive side effect of reducing costs in the healthcare system.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.3389/fmolb.2024.1467366
Elina Nürnberg, Mario Vitacolonna, Roman Bruch, Markus Reischl, Rüdiger Rudolf, Simeon Sauer
3D cell culture models replicate tissue complexity and aim to study cellular interactions and responses in a more physiologically relevant environment compared to traditional 2D cultures. However, the spherical structure of these models makes it difficult to extract meaningful data, necessitating advanced techniques for proper analysis. In silico simulations enhance research by predicting cellular behaviors and therapeutic responses, providing a powerful tool to complement experimental approaches. Despite their potential, these simulations often require advanced computational skills and significant resources, which creates a barrier for many researchers. To address these challenges, we developed an accessible pipeline using open-source software to facilitate virtual tissue simulations. Our approach employs the Cellular Potts Model, a versatile framework for simulating cellular behaviors in tissues. The simulations are constructed from real world 3D image stacks of cancer spheroids, ensuring that the virtual models are rooted in experimental data. By introducing a new metric for parameter optimization, we enable the creation of realistic simulations without requiring extensive computational expertise. This pipeline benefits researchers wanting to incorporate computational biology into their methods, even if they do not possess extensive expertise in this area. By reducing the technical barriers associated with advanced computational modeling, our pipeline enables more researchers to utilize these powerful tools. Our approach aims to foster a broader use of in silico methods in disease research, contributing to a deeper understanding of disease biology and the refinement of therapeutic interventions.
{"title":"From in vitro to in silico: a pipeline for generating virtual tissue simulations from real image data","authors":"Elina Nürnberg, Mario Vitacolonna, Roman Bruch, Markus Reischl, Rüdiger Rudolf, Simeon Sauer","doi":"10.3389/fmolb.2024.1467366","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1467366","url":null,"abstract":"3D cell culture models replicate tissue complexity and aim to study cellular interactions and responses in a more physiologically relevant environment compared to traditional 2D cultures. However, the spherical structure of these models makes it difficult to extract meaningful data, necessitating advanced techniques for proper analysis. In silico simulations enhance research by predicting cellular behaviors and therapeutic responses, providing a powerful tool to complement experimental approaches. Despite their potential, these simulations often require advanced computational skills and significant resources, which creates a barrier for many researchers. To address these challenges, we developed an accessible pipeline using open-source software to facilitate virtual tissue simulations. Our approach employs the Cellular Potts Model, a versatile framework for simulating cellular behaviors in tissues. The simulations are constructed from real world 3D image stacks of cancer spheroids, ensuring that the virtual models are rooted in experimental data. By introducing a new metric for parameter optimization, we enable the creation of realistic simulations without requiring extensive computational expertise. This pipeline benefits researchers wanting to incorporate computational biology into their methods, even if they do not possess extensive expertise in this area. By reducing the technical barriers associated with advanced computational modeling, our pipeline enables more researchers to utilize these powerful tools. Our approach aims to foster a broader use of <jats:italic>in silico</jats:italic> methods in disease research, contributing to a deeper understanding of disease biology and the refinement of therapeutic interventions.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The differentiation of vascular endothelial cells and the formation of new blood vessels are inseparable from the energy supply and regulation of metabolism. The budding of blood vessels is a starting point of glycolysis pathway in angiogenesis. Phosphofructokinase-2/fructose 2,6-biophosphatase 3 (PFKFB3), a key rate-limiting enzyme in glycolysis, exhibits strong kinase activity. Inhibition of PFKFB3 can reduce the rate of glycolysis, thereby inhibiting the budding of blood vessels, resulting in inhibition of pathological angiogenesis. In this review, the role of PFKFB3 in the angiogenesis of inflammatory diseases was summarized, and the endothelial inflammatory diseases associated with PFKFB3 were reviewed.
{"title":"Pathogenic role of PFKFB3 in endothelial inflammatory diseases","authors":"Ling Zhou, Juan Li, Juanjuan Wang, Xuping Niu, Junqin Li, Kaiming Zhang","doi":"10.3389/fmolb.2024.1454456","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1454456","url":null,"abstract":"The differentiation of vascular endothelial cells and the formation of new blood vessels are inseparable from the energy supply and regulation of metabolism. The budding of blood vessels is a starting point of glycolysis pathway in angiogenesis. Phosphofructokinase-2/fructose 2,6-biophosphatase 3 (PFKFB3), a key rate-limiting enzyme in glycolysis, exhibits strong kinase activity. Inhibition of PFKFB3 can reduce the rate of glycolysis, thereby inhibiting the budding of blood vessels, resulting in inhibition of pathological angiogenesis. In this review, the role of PFKFB3 in the angiogenesis of inflammatory diseases was summarized, and the endothelial inflammatory diseases associated with PFKFB3 were reviewed.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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