Frontiers in Molecular Biosciences最新文献

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Novel insights into cuproptosis inducers and inhibitors. 铜增生诱导剂和抑制剂的新见解。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-26 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1477971
Ligang Zhang, Ruiting Deng, Lian Liu, Hongli Du, Dongsheng Tang
{"title":"Novel insights into cuproptosis inducers and inhibitors.","authors":"Ligang Zhang, Ruiting Deng, Lian Liu, Hongli Du, Dongsheng Tang","doi":"10.3389/fmolb.2024.1477971","DOIUrl":"10.3389/fmolb.2024.1477971","url":null,"abstract":"<p><p>Cuproptosis is a new pattern of Cu-dependent cell death distinct from classic cell death pathways and characterized by aberrant lipoylated protein aggregation in TCA cycle, Fe-S cluster protein loss, HSP70 elevation, proteotoxic and oxidative stress aggravation. Previous studies on Cu homeostasis and Cu-induced cell death provide a great basis for the discovery of cuproptosis. It has gradually gathered enormous research interests and large progress has been achieved in revealing the metabolic pathways and key targets of cuproptosis, due to its role in mediating some genetic, neurodegenerative, cardiovascular and tumoral diseases. In terms of the key targets in cuproptosis metabolic pathways, they can be categorized into three types: oxidative stress, mitochondrial respiration, ubiquitin-proteasome system. And strategies for developing cuproptosis inducers and inhibitors involved in these targets have been continuously improved. Briefly, based on the essential cuproptosis targets and metabolic pathways, this paper classifies some relevant inducers and inhibitors including small molecule compounds, transcription factors and ncRNAs with the overview of principle, scientific and medical application, in order to provide reference for the cuproptosis study and target therapy in the future.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1477971"},"PeriodicalIF":3.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806301","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}
引用次数: 0
A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer. 一种预测膀胱癌预后和治疗反应的新坏死相关基因标记。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-25 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1493411
Dongnuan Yao, Weitao Yu, Xueming Ma, Junqiang Tian
{"title":"A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer.","authors":"Dongnuan Yao, Weitao Yu, Xueming Ma, Junqiang Tian","doi":"10.3389/fmolb.2024.1493411","DOIUrl":"10.3389/fmolb.2024.1493411","url":null,"abstract":"<p><strong>Background: </strong>Necroptosis, a form of programmed inflammatory cell death, plays a crucial role in tumor development, necrosis, metastasis, and immune response. This study aimed to explore the role of necroptosis in BLCA and construct a new prognostic model to guide clinical treatment and predict individualized treatment response.</p><p><strong>Methods: </strong>The transcriptome profiling and the corresponding clinical data of BLCA patients were obtained from the Cancer Genome Atlas database (TCGA) and GEO databases. Univariate, multivariate and LASSO Cox regression analyses were used to identify and construct prognostic features associated with necroptosis. We constructed and validated a prognostic model associated with the patient's overall survival (OS). A nomogram was established to predict the survival rates of BLCA patients. Finally, the correlation between risk scores and tumor immune microenvironment, somatic mutations, immunotherapy, and chemotherapy was comprehensively analyzed.</p><p><strong>Results: </strong>The study found two distinct NRG clusters and three gene subtypes, with significant differences in pathway enrichment and immune cell infiltration associated with different NRG clusters in the TME. In addition, we screened out six necroptosis prognosis-related genes (including PPP2R3A; CERCAM; PIK3IP1; CNTN1; CES1 and CD96) to construct a risk score prognostic model. Significant differences in overall survival rate, immune cell infiltration status, and somatic mutations existed between the high and low-risk scores in BLCA patients. Finally, drug sensitivity analysis showed that high-risk patients benefited more from immunotherapy and chemotherapy drugs.</p><p><strong>Conclusion: </strong>This study explores the importance of necroptosis in the prognosis of patients with BLCA, and the prognostic features associated with necroptosis that we identified can serve as new biomarkers to help develop more precise treatment strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1493411"},"PeriodicalIF":3.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800006","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}
引用次数: 0
Precision-engineered PROTACs minimize off-tissue effects in cancer therapy. 精密工程PROTACs在癌症治疗中最大限度地减少了组织外效应。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-22 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1505255
Jianghua Shi, Luo Wang, Xuanwei Zeng, Chengzhi Xie, Zhaowei Meng, Anahit Campbell, Lulu Wang, Heli Fan, Huabing Sun
{"title":"Precision-engineered PROTACs minimize off-tissue effects in cancer therapy.","authors":"Jianghua Shi, Luo Wang, Xuanwei Zeng, Chengzhi Xie, Zhaowei Meng, Anahit Campbell, Lulu Wang, Heli Fan, Huabing Sun","doi":"10.3389/fmolb.2024.1505255","DOIUrl":"10.3389/fmolb.2024.1505255","url":null,"abstract":"<p><p>Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain a major challenge, leading to toxicity in healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated in tumor environments, and E3 ligase overexpression strategies. Innovations such as PEGylation and nanotechnology also play a role in optimizing PROTAC efficacy. These developments hold promise for safer, more effective cancer therapies, though challenges remain for clinical translation.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1505255"},"PeriodicalIF":3.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800008","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}
引用次数: 0
Visualization of argininosuccinate synthetase by in silico analysis: novel insights into citrullinemia type I disorders. 通过硅分析实现精氨酸琥珀酸合成酶的可视化:对瓜氨酸血症 I 型疾病的新见解。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-22 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1482773
Xia Gu, Wenhui Mo, Guiying Zhuang, Congcong Shi, Tao Wei, Jinze Zhang, Chiaowen Tu, Yao Cai, Biwen Liao, Hu Hao
{"title":"Visualization of argininosuccinate synthetase by <i>in silico</i> analysis: novel insights into citrullinemia type I disorders.","authors":"Xia Gu, Wenhui Mo, Guiying Zhuang, Congcong Shi, Tao Wei, Jinze Zhang, Chiaowen Tu, Yao Cai, Biwen Liao, Hu Hao","doi":"10.3389/fmolb.2024.1482773","DOIUrl":"10.3389/fmolb.2024.1482773","url":null,"abstract":"<p><strong>Background: </strong>Citrullinemia type I disorders (CTLN1) is a genetic metabolic disease caused by argininosuccinate synthetase (ASS1) gene mutation. To date, the human genome mutation database has documented over 100 variants of the ASS1 gene. This study reported a novel deletion-insertion variant of ASS1 gene and employed various prediction tools to determine its pathogenicity.</p><p><strong>Methods: </strong>We reported a case of early-onset CTLN1. Whole exome sequencing was conducted to identify genetic mutations. We employed various structure prediction tools to generate accurate 3D models and utilized computational biology tools to elucidate the disparities between the wild-type and mutant proteins.</p><p><strong>Results: </strong>The patient was characterized by severe clinical manifestations, including poor responsiveness, lethargy, convulsions, and cardiac arrest. Notably, the patient exhibited significantly elevated blood ammonia levels (655 μmol/L; normal reference: 10-30 μmol/L) and increased citrulline concentrations (936 μmol/L; normal reference: 5-25 μmol/L). Whole exome sequencing revealed a in-frame deletion-insertion mutation <i>c.1128_1134delinsG</i> in the ASS1 gene of unknown significance, which has not been previously reported. Our finding indicated that the C- terminal helix domain of the mutant protein structure, which was an important structure for ASS1 protein to form protein tetramers, was indeed more unstable than that of the wild-type protein structure.</p><p><strong>Conclusion: </strong>Through conducting an in silico analysis on this unique in-frame deletion-insertion variant of ASS1, our aim was to enhance understanding regarding its structure-function relationship as well as unraveling the molecular mechanism underlying CTLN1.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1482773"},"PeriodicalIF":3.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799977","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}
引用次数: 0
Bacteriophage RNA polymerases: catalysts for mRNA vaccines and therapeutics. 噬菌体RNA聚合酶:mRNA疫苗和疗法的催化剂。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1504876
Adithya Nair, Zoltán Kis
{"title":"Bacteriophage RNA polymerases: catalysts for mRNA vaccines and therapeutics.","authors":"Adithya Nair, Zoltán Kis","doi":"10.3389/fmolb.2024.1504876","DOIUrl":"10.3389/fmolb.2024.1504876","url":null,"abstract":"<p><p>Decades of research on bacteriophage-derived RNA polymerases (RNAPs) were vital for synthesizing mRNA using the <i>in vitro</i> transcription (IVT) reaction for vaccines during the COVID-19 pandemic. The future success of mRNA-based products relies on the efficiency of its manufacturing process. mRNA manufacturing is a platform technology that complements the quality by design (QbD) paradigm. We applied the QbD framework in combination with key mechanistic insights on RNAP to assess the impact of IVT-associated critical process parameters (CPPs) and critical material attributes (CMAs) on the critical quality attributes (CQAs) of the mRNA drug substance and on manufacturing key performance indicators (KPIs). We also summarize the structure-function relationship of T7 RNAP and its engineered mutants aimed at enhancing the critical production of low-immunogenic mRNA therapeutics. Alternatives to the current set of standard RNAPs in large-scale IVTs are also discussed based on a phylogenetic background. Finally, the review dives into the economic implications of improving mRNA manufacturing based on the main enzyme, T7 RNAP, used to synthesize the mRNA drug substance. The review concludes by mapping the relationship between various CMAs and CPPs with different phases of the IVT reaction from a QbD perspective.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1504876"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784782","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}
引用次数: 0
Circulating GLAST+ EVs are increased in amyotrophic lateral sclerosis. 肌萎缩性侧索硬化症患者循环GLAST+ ev增加。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1507498
Davide Raineri, Fabiola De Marchi, Beatrice Vilardo, Camilla Barbero Mazzucca, Lorenza Scotti, Natasa Kustrimovic, Letizia Mazzini, Giuseppe Cappellano, Annalisa Chiocchetti
{"title":"Circulating GLAST<sup>+</sup> EVs are increased in amyotrophic lateral sclerosis.","authors":"Davide Raineri, Fabiola De Marchi, Beatrice Vilardo, Camilla Barbero Mazzucca, Lorenza Scotti, Natasa Kustrimovic, Letizia Mazzini, Giuseppe Cappellano, Annalisa Chiocchetti","doi":"10.3389/fmolb.2024.1507498","DOIUrl":"10.3389/fmolb.2024.1507498","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, hallmarked by the gradual deterioration of motor neurons, culminating in muscle weakness and fatal paralysis. The exact etiology of ALS remains elusive, and there is a critical need for reliable biomarkers to aid in diagnosis and monitoring of disease progression. Extracellular vesicles (EVs) have emerged as promising candidates for biomarker discovery in neurodegenerative diseases such as ALS, giving access to pathologically relevant tissues otherwise typically challenging or invasive to sample. Indeed, EVs can derive by many cell types within the central nervous system, cross the blood-brain barrier and reach the blood, where they can be easily measured. One of the central mechanisms implicated in ALS pathology is glutamate excitotoxicity, which involves excessive glutamate accumulation due to impaired uptake by astrocytes and other glial cells, leading to neuronal damage. GLAST is a key glutamate transporter responsible for maintaining extracellular gluta-mate levels, and its dysregulation is thought to contribute significantly to ALS development and associated neuropathogenesis. Here, we applied a quick and validated method, to evaluate GLAST<sup>+</sup> EVs in ALS patients' plasma and age-matched healthy controls. We found an increase in GLAST<sup>+</sup> EVs that holds promise for uncovering novel diagnostic and therapeutic avenues in ALS research.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1507498"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784786","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}
引用次数: 0
Extended range proteomic analysis of blood plasma from schizophrenia patients. 精神分裂症患者血浆扩展范围蛋白质组学分析。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1483933
Denis V Petrovskiy, Tatiana V Butkova, Kirill S Nikolsky, Arthur T Kopylov, Valeriya I Nakhod, Liudmila I Kulikova, Kristina A Malsagova, Nikolai D Kibrik, Vladimir R Rudnev, Alexander A Izotov, Anna L Kaysheva
{"title":"Extended range proteomic analysis of blood plasma from schizophrenia patients.","authors":"Denis V Petrovskiy, Tatiana V Butkova, Kirill S Nikolsky, Arthur T Kopylov, Valeriya I Nakhod, Liudmila I Kulikova, Kristina A Malsagova, Nikolai D Kibrik, Vladimir R Rudnev, Alexander A Izotov, Anna L Kaysheva","doi":"10.3389/fmolb.2024.1483933","DOIUrl":"10.3389/fmolb.2024.1483933","url":null,"abstract":"<p><strong>Introduction: </strong>The high prevalence of schizophrenia worldwide makes it necessary to proceed from subjective assessment of patient's clinical symptoms in diagnosis making to searching for circulating blood biomarkers. On the one hand, searching for molecular markers and targets for therapeutics will make it possible to refine and detail the molecular mechanisms of pathology development, while on the other hand, it will offer new opportunities for elaborating novel approaches to disease diagnosis and enhance efficacy and timeliness of drug therapy.</p><p><strong>Methods: </strong>In this study, we performed an extended-range proteomic analysis of plasma samples collected from 48 study subjects with confirmed diagnosis of schizophrenia and 50 healthy volunteers. The high-resolution tandem mass spectra recorded in the data-dependent acquisition mode were analyzed using the MaxQuant algorithm for the library of known protein sequences and the PowerNovo algorithm for <i>de novo</i> protein sequencing.</p><p><strong>Results: </strong>It was demonstrated that both strategies show similar results for high-abundance proteins (≥1 μg/mL). For mid-abundance (10 ng/mL - 1 μg/mL) and low-abundance (<10 ng/mL) proteins, the results obtained by the two search strategies complement each other.</p><p><strong>Discussion: </strong>Group-specific proteins for the samples of schizophrenia patients were identified, presumably being involved in synaptic plasticity, angiogenesis, transcriptional regulation, protein stabilization and degradation.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1483933"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784792","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}
引用次数: 0
Identification of key genes to predict response to chemoradiotherapy and prognosis in esophageal squamous cell carcinoma. 预测食管鳞状细胞癌放化疗反应和预后的关键基因鉴定。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-20 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1512715
Yingying Cui, Jing Wen, Jianhua Fu, Changsen Leng
{"title":"Identification of key genes to predict response to chemoradiotherapy and prognosis in esophageal squamous cell carcinoma.","authors":"Yingying Cui, Jing Wen, Jianhua Fu, Changsen Leng","doi":"10.3389/fmolb.2024.1512715","DOIUrl":"10.3389/fmolb.2024.1512715","url":null,"abstract":"<p><strong>Background: </strong>Chemoradiotherapy is a crucial treatment modality for esophageal squamous cell carcinoma (ESCC). This study aimed to identify chemoradiotherapy sensitivity-related genes and analyze their prognostic value and potential associations with the tumor microenvironment in ESCC.</p><p><strong>Methods: </strong>Utilizing the Gene Expression Omnibus database, we identified differentially expressed genes between ESCC patients who achieved complete and incomplete pathological responses following chemoradiotherapy. Prognostic genes were then screened, and key genes associated with chemoradiotherapy sensitivity were determined using random survival forest analysis. We examined the relationships between key genes, infiltrating immune cells, and immunoregulatory genes. Additionally, drug sensitivity and enrichment analyses were conducted to assess the impact of key genes on chemotherapy responses and signaling pathways. A prognostic nomogram for ESCC was developed incorporating key genes, and its effectiveness was evaluated. Genome-wide association study data were employed to investigate chromosomal pathogenic regions associated with key genes.</p><p><strong>Results: </strong>Three key genes including <i>ATF2</i>, <i>SLC27A5</i>, and <i>ALOXE3</i> were identified. These genes can predict the sensitivity of ESCC patients to neoadjuvant chemoradiotherapy and hold significant clinical relevance in prognostication. These genes were also found to be significantly correlated with certain immune cells and immunoregulatory genes within the tumor microenvironment and were involved in critical tumor-related signaling pathways, including the epithelial-mesenchymal transition and P53 pathways. A nomogram was established to predict the prognosis of ESCC by integrating key genes with clinical stages, demonstrating favorable predictability and reliability.</p><p><strong>Conclusion: </strong>This study identified three key genes that predict chemoradiotherapy sensitivity and prognosis and are involved in multiple tumor-related biological processes in ESCC. These findings provide predictive biomarkers for chemoradiotherapy response and support the development of individualized treatment strategies for ESCC patients.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1512715"},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779271","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}
引用次数: 0
Serum beta2-microglobulin and peripheral blood eosinophils for the assessment of severity and prognosis with omicron variant COVID-19 infection. 血清β -微球蛋白和外周血嗜酸性粒细胞对组粒变异型COVID-19感染严重程度和预后的评估
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-20 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1476080
Jie Tan, Hanxi Fang, Xiao Hu, Ming Yue, Junling Yang
{"title":"Serum beta2-microglobulin and peripheral blood eosinophils for the assessment of severity and prognosis with omicron variant COVID-19 infection.","authors":"Jie Tan, Hanxi Fang, Xiao Hu, Ming Yue, Junling Yang","doi":"10.3389/fmolb.2024.1476080","DOIUrl":"10.3389/fmolb.2024.1476080","url":null,"abstract":"<p><strong>Background: </strong>The Omicron variant's high transmissibility has made it the most widespread novel coronavirus variant. Elevated serum β2-MG levels from viral infections and EOS' role in viral clearance have garnered attention. However, their predictive value for Omicron's severity and prognosis needs further exploration.</p><p><strong>Methods: </strong>This retrospective study included 424 patients with confirmed COVID-19 Omicron variant admitted to the Second Hospital of Jilin University in Changchun, China, of whom 128 experienced in-hospital mortality. Patients were divided into high and low groups according to β2-MG and EOS levels; the relationship between disease severity and patient prognosis was analyzed.</p><p><strong>Results: </strong>Our findings showed that severe-to-critical Omicron patients had higher β2-MG levels than mild-normal patients. Conversely, EOS levels were higher in mild-moderate cases. Both β2-MG and EOS levels normalized when Omicron patients tested negative for nucleic acid. Deceased Omicron patients had significantly lower pre-mortem EOS levels. Elevated β2-MG and lower EOS levels correlated with reduced overall survival. Multivariate COX regression analysis indicated that elevated β2-MG was an independent adverse prognostic factor for Omicron patients.</p><p><strong>Conclusion: </strong>High serum β2-MG levels and low eosinophil levels upon admission correlate with omicron variant severity and prognosis. β2-MG is an independent risk factor for poor outcomes in omicron patients.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1476080"},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779532","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}
引用次数: 0
Protein-free domains in native and ferroptosis-driven oxidized cell membranes: a molecular dynamics study of biophysical properties and doxorubicin uptake. 原生和死铁驱动氧化细胞膜中的无蛋白结构域:生物物理特性和阿霉素摄取的分子动力学研究。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-14 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1494257
Yaser Shabanpour, Behnam Hajipour-Verdom, Parviz Abdolmaleki, Mozhgan Alipour
{"title":"Protein-free domains in native and ferroptosis-driven oxidized cell membranes: a molecular dynamics study of biophysical properties and doxorubicin uptake.","authors":"Yaser Shabanpour, Behnam Hajipour-Verdom, Parviz Abdolmaleki, Mozhgan Alipour","doi":"10.3389/fmolb.2024.1494257","DOIUrl":"10.3389/fmolb.2024.1494257","url":null,"abstract":"<p><p>Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxidation of polyunsaturated fatty acids (PUFAs). Despite its significance, the precise molecular mechanisms underlying ferroptosis remain elusive, particularly concerning their impact on membrane properties. This study aimed to investigate the biophysical changes in plasma membranes due to lipid peroxidation during ferroptosis and their impact on the uptake of doxorubicin (DOX), a potent anticancer agent linked to ferroptosis. Using all-atom molecular dynamics simulations, we compared native red blood cell membranes (protein-free domains) with a ferroptosis model, in which PUFAs were replaced with hydroperoxide derivatives. Our findings reveal that the ferroptotic membrane exhibits decreased thickness and increased lipid area while maintaining overall integrity. The hydroperoxide groups localized in the disordered tail regions, enhancing tail mobility and facilitating hydrogen bonding. Lipid lateral diffusion was significantly altered, both layers of the ferroptotic membrane exhibited slower diffusion rates compared to the native membrane. Furthermore, lipid oxidation affected diffusion activation energies. Importantly, we found that DOX could penetrate the oxidized ferroptosis membrane with a lower free-energy barrier (∆G<sub>PB</sub>) of approximately 38 kJ.mol<sup>-1</sup>. Consequently, DOX's permeability was approximately seven orders of magnitude higher than that of the native membrane. In summary, lipid peroxidation during ferroptosis induces extensive structural and dynamic changes, influencing membrane behavior and potentially offering insights that could inform future therapeutic strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1494257"},"PeriodicalIF":3.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750366","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}
引用次数: 0
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