Experimental Biology and Medicine最新文献_第2页

Berberine alleviates AGEs-induced ferroptosis by activating NRF2 in the skin of diabetic mice. 小檗碱通过激活糖尿病小鼠皮肤NRF2减轻衰老诱导的铁下垂。

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-12-13 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10280

Chunjie Jiang, Guojuan Lao, Jianmin Ran, Ping Zhu

{"title":"Berberine alleviates AGEs-induced ferroptosis by activating NRF2 in the skin of diabetic mice.","authors":"Chunjie Jiang, Guojuan Lao, Jianmin Ran, Ping Zhu","doi":"10.3389/ebm.2024.10280","DOIUrl":"10.3389/ebm.2024.10280","url":null,"abstract":"Advanced glycation end products (AGEs) have adverse effects on the development of diabetic complications. Berberine (BBR), a natural alkaloid, has demonstrated its ability to promote the delayed healing of skin wounds. However, the impact of BBR on AGEs-induced ferroptosis in skin cells and the underlying molecular mechanisms remains unexplored. This study investigated the involvement of ferroptosis in AGEs-induced keratinocyte death, and the impact of BBR on ferroptosis in a db/db mouse model with long-term hyperglycemia was elucidated. A remarkable reduction in cell viability was observed along with increased malondialdehyde (MDA) production in AGEs-induced HaCaT cells. Intracellular reactive oxygen species (ROS) and iron levels were elevated in cells exposed to AGEs. Meanwhile, the protein expression of glutathione peroxidase 4 (GPX4) and ferritin light chain (FTL) was significantly decreased in AGEs-treated cells. However, pretreatment with BBR markedly protected cell viability and inhibited MDA levels, attenuating the intracellular ROS and iron levels and increased expression of GPX4 and FTL in vitro. Significantly diminished antiferroptotic effects of BBR on AGEs-treated keratinocytes were observed upon the knockdown of the nuclear factor E2-related factor 2 (NRF2) gene. In vivo, GPX4, FTL, and FTH expression in the epidermis of diabetic mice was significantly reduced, accompanied by enhanced lipid peroxidation. Treatment with BBR effectively rescued lipid peroxidation accumulation and upregulated GPX4, FTL, FTH, and NRF2 levels in diabetic skin. Collectively, the findings indicate that ferroptosis may play a significant role in AGEs-induced keratinocyte death. BBR protects diabetic keratinocytes against ferroptosis, partly by activating NRF2.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10280"},"PeriodicalIF":2.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902336","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

Dysregulated transfer RNA-derived small RNAs as potential gastric cancer biomarkers. 失调的转移rna衍生的小rna作为潜在的胃癌生物标志物。

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-12-13 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10170

Jie Yuan, Wenchao Gu, Tianxin Xu, Yan Zhang, Lei Shen, Jianliang Yan, Xi Guan, Haidan Chu, Ruoyu Yuan, Shaoqing Ju

{"title":"Dysregulated transfer RNA-derived small RNAs as potential gastric cancer biomarkers.","authors":"Jie Yuan, Wenchao Gu, Tianxin Xu, Yan Zhang, Lei Shen, Jianliang Yan, Xi Guan, Haidan Chu, Ruoyu Yuan, Shaoqing Ju","doi":"10.3389/ebm.2024.10170","DOIUrl":"10.3389/ebm.2024.10170","url":null,"abstract":"Gastric cancer (GC) is the kind of carcinoma that has the highest rates of morbidity and death worldwide. In the early stages of GC, there is currently an absence of sensitive and specific biomarkers. The newly-discovered class of non-coding RNAs (ncRNAs) known as transfer RNA-derived small RNAs (tsRNAs) is highly expressed in bodily fluids and neoplastic cells. High-throughput sequencing was initially employed to identify differentially expressed tsRNAs in early GC patients, followed by validation in patient serum, GC tissues, and cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). We identified dysregulated tsRNAs (the up-regulated tsRNAs included tRF-31-PNR8YP9LON4VD, tRF-30-MIF91SS2P4FI, and tRF-30-IK9NJ4S2I7L7, whereas the down-regulated tsRNAs included tRF-38-W6RM7KYUPRENRHD2, tRF-37-LBRY73W0K5KKOV2, tRF-36-JB59V3WD8YQ84VD, tRF-25-MBQ4NKKQBR, and tRF-36-0KFMNKYUHRF867D) in GC, and we verified that the serum of patients, GC cells and tissues both consistently expressed these tsRNAs. Additionally, GC patients' serum had considerably greater expression levels of the three up-regulated tsRNAs than did healthy controls. Receiver operating characteristic (ROC) curve analysis demonstrated that the sensitivity and specificity of the three up-regulated tsRNAs were superior to those of CEA, CA199, and CA724 in the process of diagnosing GC, particularly in its early stages. This suggests that tsRNAs have great diagnostic efficacy and potential as new \"liquid biopsy\" biomarkers for the diagnosis of GC. Using bioinformatics software, we predicted that dysregulation of tsRNAs may be a potential regulatory mechanism for the development of GC.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10170"},"PeriodicalIF":2.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902351","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

Enhancing pharmacogenomic data accessibility and drug safety with large language models: a case study with Llama3.1. 利用大型语言模型增强药物基因组学数据可及性和药物安全性：以Llama3.1为例

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-12-03 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10393

Dan Li, Leihong Wu, Ying-Chi Lin, Ho-Yin Huang, Ebony Cotton, Qi Liu, Ru Chen, Ruihao Huang, Yifan Zhang, Joshua Xu

{"title":"Enhancing pharmacogenomic data accessibility and drug safety with large language models: a case study with Llama3.1.","authors":"Dan Li, Leihong Wu, Ying-Chi Lin, Ho-Yin Huang, Ebony Cotton, Qi Liu, Ru Chen, Ruihao Huang, Yifan Zhang, Joshua Xu","doi":"10.3389/ebm.2024.10393","DOIUrl":"10.3389/ebm.2024.10393","url":null,"abstract":"Pharmacogenomics (PGx) holds the promise of personalizing medical treatments based on individual genetic profiles, thereby enhancing drug efficacy and safety. However, the current landscape of PGx research is hindered by fragmented data sources, time-consuming manual data extraction processes, and the need for comprehensive and up-to-date information. This study aims to address these challenges by evaluating the ability of Large Language Models (LLMs), specifically Llama3.1-70B, to automate and improve the accuracy of PGx information extraction from the FDA Table of Pharmacogenomic Biomarkers in Drug Labeling (FDA PGx Biomarker table), which is well-structured with drug names, biomarkers, therapeutic area, and related labeling texts. Our primary goal was to test the feasibility of LLMs in streamlining PGx data extraction, as an alternative to traditional, labor-intensive approaches. Llama3.1-70B achieved 91.4% accuracy in identifying drug-biomarker pairs from single labeling texts and 82% from mixed texts, with over 85% consistency in aligning extracted PGx categories from FDA PGx Biomarker table and relevant scientific abstracts, demonstrating its effectiveness for PGx data extraction. By integrating data from diverse sources, including scientific abstracts, this approach can support pharmacologists, regulatory bodies, and healthcare researchers in updating PGx resources more efficiently, making critical information more accessible for applications in personalized medicine. In addition, this approach shows potential of discovering novel PGx information, particularly of underrepresented minority ethnic groups. This study highlights the ability of LLMs to enhance the efficiency and completeness of PGx research, thus laying a foundation for advancements in personalized medicine by ensuring that drug therapies are tailored to the genetic profiles of diverse populations.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10393"},"PeriodicalIF":2.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846286","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

Integrating artificial intelligence in strabismus management: current research landscape and future directions. 将人工智能融入斜视管理：研究现状与未来方向。

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-11-25 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10320

Dawen Wu, Xi Huang, Liang Chen, Peixian Hou, Longqian Liu, Guoyuan Yang

引用次数: 0

Association of immunity-related gene SNPs with Alzheimer's disease. 免疫相关基因snp与阿尔茨海默病的关联

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-11-22 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10303

Nisrine Bissar, Rayan Kassir, Ali Salami, Said El Shamieh

{"title":"Association of immunity-related gene SNPs with Alzheimer's disease.","authors":"Nisrine Bissar, Rayan Kassir, Ali Salami, Said El Shamieh","doi":"10.3389/ebm.2024.10303","DOIUrl":"10.3389/ebm.2024.10303","url":null,"abstract":"Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive decline. Genetic factors have been implicated in disease susceptibility as its etiology remains multifactorial. The CD33 and the HLA-DRB1 genes, involved in immune responses, have emerged as potential candidates influencing AD risk. In this study, 644 Lebanese individuals, including 127 AD patients and 250 controls, were genotyped, by KASP assay, for six SNPs selected from the largest GWAS study in 2021. Logistic regression analysis assessed the association between SNP genotypes and AD risk, adjusting for potential confounders. Among the six SNPs analyzed, rs1846190G>A in HLA-DRB1 and rs1354106T>G in CD33 showed significant associations with AD risk in the Lebanese population (p < 0.05). Carriers of the AG and AA genotypes of rs1846190 in HLA-DRB1 exhibited a protective effect against AD (AG: OR = 0.042, p = 0.026; AA: OR = 0.052, p = 0.031). The GT genotype of rs1354106T>G in CD33 was also associated with reduced risk (OR = 0.173, p = 0.005). Following Bonferroni correction, a significant correlation of rs1354106T > G with AD risk was established. Our results might highlight the complex interplay between genetic and immunological factors contributing to the development of the disease.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10303"},"PeriodicalIF":2.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800116","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

Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail model. 通过操纵YAP在小鼠尾部模型中进行淋巴水肿治疗来工程ADSCs。

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-11-20 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10295

Liru Hu, Nian Zhang, Chengzhi Zhao, Jian Pan

{"title":"Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail model.","authors":"Liru Hu, Nian Zhang, Chengzhi Zhao, Jian Pan","doi":"10.3389/ebm.2024.10295","DOIUrl":"10.3389/ebm.2024.10295","url":null,"abstract":"Secondary lymphedema is a chronic disease associated with deformity of limbs and dysfunction; however, conventional therapies are not curative. Adipose-derived stem cells (ADSCs) based therapy is a promising way, but a single transplantation of ADSCs has limited efficacy. In this study, ADSCs were engineered in vitro and then transplanted into the site of lymphedema. Yes-associated protein (YAP), a crucial regulator of Hippo pathway, plays an important role in regulating stem cell functions. We examined the YAP expression in a mouse tail lymphedema model, and found that transplanted ADSCs exhibited high expression level of YAP and a large number of YAP positive cells existed in lymphedema environment. In vitro, the downregulation of YAP in ADSCs resulted in higher expression levels of genes related to lymphangiogenesis such as Lyve-1, VEGFR-3 and Prox-1. In vivo, YAP-engineered ADSCs generated abundant VEGFR-3-positive lymphatic vessels and significantly improved subcutaneous fibrosis. These results indicated that the transplantation of pre-engineered ADSCs by manipulating YAP is a promising strategy for lymphatic reconstruction.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10295"},"PeriodicalIF":2.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779655","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

Predicting severe COVID-19 using readily available admission indicators: SpO2/FiO2 ratio, comorbidity index, and gender. 使用现成的入院指标预测重症COVID-19: SpO2/FiO2比率、合并症指数和性别。

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-11-20 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10193

Luan D Vu, Rebecca C Christofferson, Hollis R O'Neal, Diana Hamer, Anh T Q Phan, Katie M Vance, E A Turner, Avinash Kumar, Ibrahim Musa Yola, Natalie Lim, Beverly Ogden, Stephania A Cormier

{"title":"Predicting severe COVID-19 using readily available admission indicators: SpO2/FiO2 ratio, comorbidity index, and gender.","authors":"Luan D Vu, Rebecca C Christofferson, Hollis R O'Neal, Diana Hamer, Anh T Q Phan, Katie M Vance, E A Turner, Avinash Kumar, Ibrahim Musa Yola, Natalie Lim, Beverly Ogden, Stephania A Cormier","doi":"10.3389/ebm.2024.10193","DOIUrl":"10.3389/ebm.2024.10193","url":null,"abstract":"The focus of this study was to identify risk factors for severe and critical COVID-19, evaluate local respiratory immune responses to SARS-CoV-2 infection, and develop a prognostic tool for COVID-19 severity using accessible early indicators. Using nasopharyngeal swab samples from hospitalized patients with COVID-19 of varying severity during the first wave of the pandemic from March to May 2020 in Louisiana, we evaluated the association between COVID-19 severity and viral load, respiratory immune mediators, and demographic/clinical factors. We found that the SpO2/FiO2 ratio at triage, total comorbidity burden (represented by Charlson Comorbidity Index), and gender were significantly associated with COVID-19 severity. Using these early significant indicators, we developed a prognostic tool for COVID-19 severity that is simple and convenient. Additionally, our study demonstrated that elevated levels of respiratory immune mediators, including IL-10, IL-6, MCP-1, and MCP-3, were significantly associated with COVID-19 severity. We also found that viral load at the time of admission was associated with disease severity. Our findings highlight the feasibility and importance of evaluating the humoral component of local mucosal immune responses and viral load at the infected site using convenient nasopharyngeal swab samples, which could be an effective method to understand the relationship between viral infection and immune responses at the early stages of infection. Our proposed prognostic tool has the potential to be useful for COVID-19 management in clinical settings, as it utilizes accessible and easy-to-collect variables at the time of admission.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10193"},"PeriodicalIF":2.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779664","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

Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice. 神经炎症是雄性镰状细胞小鼠社会压力诱导的认知缺陷发展的基础。

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-11-19 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10361

S'Dravious A DeVeaux, Sofiya Vyshnya, Katherine Propsom, Oluwabukola T Gbotosho, Asem S Singh, Robert Z Horning, Mihika Sharma, Anil G Jegga, Liang Niu, Edward A Botchwey, Hyacinth I Hyacinth

{"title":"Neuroinflammation underlies the development of social stress induced cognitive deficit in male sickle cell mice.","authors":"S'Dravious A DeVeaux, Sofiya Vyshnya, Katherine Propsom, Oluwabukola T Gbotosho, Asem S Singh, Robert Z Horning, Mihika Sharma, Anil G Jegga, Liang Niu, Edward A Botchwey, Hyacinth I Hyacinth","doi":"10.3389/ebm.2024.10361","DOIUrl":"10.3389/ebm.2024.10361","url":null,"abstract":"Cognitive deficit is a debilitating complication of sickle cell disease (SCD), with a multifactorial etiopathogenesis. Here we show that neuroinflammation and dysregulation in lipidomics and transcriptomics profiles are major underlying mechanisms of social stress-induced cognitive deficit in SCD. Male Townes sickle cell (SS) mice and controls (AA) were exposed to social stress using the repeat social defeat (RSD) paradigm concurrently with or without treatment with minocycline. Mice were tested for cognitive deficit using novel object recognition and fear conditioning tests. SS mice exposed to RSD without treatment had worse performance on cognitive tests compared to SS mice exposed to RSD with treatment or to AA controls, irrespective of their RSD or treatment disposition. Additionally, compared to SS mice exposed to RSD with treatment, SS mice exposed to RSD without treatment had significantly more cellular evidence of neuroinflammation coupled with a significant shift in the differentiation of neural progenitor cells towards astrogliogenesis. Additionally, brain tissue from SS mice exposed to RSD was significantly enriched for genes associated with blood-brain barrier dysfunction, neuron excitotoxicity, inflammation, and significant dysregulation in sphingolipids important to neuronal cell processes. We demonstrate in this study that social stress induces cognitive deficit in SS mice, concurrently with neuroinflammation and lipid dysregulation.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10361"},"PeriodicalIF":2.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767650","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

STEMIN and YAP5SA, the future of heart repair? STEMIN 和 YAP5SA，心脏修复的未来？

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-10-31 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10246

Nada Bejar, Siyu Xiao, Dinakar Iyer, Azeez Muili, Adeniyi Adeleye, Bradley K McConnell, Robert J Schwartz

{"title":"STEMIN and YAP5SA, the future of heart repair?","authors":"Nada Bejar, Siyu Xiao, Dinakar Iyer, Azeez Muili, Adeniyi Adeleye, Bradley K McConnell, Robert J Schwartz","doi":"10.3389/ebm.2024.10246","DOIUrl":"10.3389/ebm.2024.10246","url":null,"abstract":"This review outlines some of the many approaches taken over a decade or more to repair damaged hearts. We showcase the recent breakthroughs in organ regeneration elicited by reprogramming factors OCT3/4, SOX2, KLF4, and C-MYC (OKSM). Transient OKSM transgene expression rejuvenated senescent organs in mice. OKSM transgenes also caused murine heart cell regeneration. A triplet alanine mutation of the N-terminus of Serum Response Factor's MADS box SRF153(A3), termed STEMIN, and the YAP mutant, YAP5SA synergized and activated OKSM and NANOG in adult rat cardiac myocytes; thus, causing rapid nuclear proliferation and blocked myocyte differentiation. In addition, ATAC seq showed induced expression of growth factor genes FGFs, BMPs, Notchs, IGFs, JAK, STATs and non-canonical Wnts. Injected STEMIN and YAP5SA synthetic modifying mRNA (mmRNA) into infarcted adult mouse hearts, brought damaged hearts back to near normal contractility without severe fibrosis. Thus, STEMIN and YAP5SA mmRNA may exert additional regenerative potential than OKSM alone for treating heart diseases.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10246"},"PeriodicalIF":2.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617714","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

Fructose metabolism is unregulated in cancers and placentae. 癌症和胎盘中的果糖代谢不受调控。

IF 2.8 4区医学

Experimental Biology and Medicine Pub Date : 2024-10-28 eCollection Date: 2024-01-01 DOI: 10.3389/ebm.2024.10200

Fuller W Bazer, Guoyao Wu, Gregory A Johnson

{"title":"Fructose metabolism is unregulated in cancers and placentae.","authors":"Fuller W Bazer, Guoyao Wu, Gregory A Johnson","doi":"10.3389/ebm.2024.10200","DOIUrl":"https://doi.org/10.3389/ebm.2024.10200","url":null,"abstract":"Fructose and lactate are present in high concentrations in uterine luminal fluid, fetal fluids and fetal blood of ungulates and cetaceans, but their roles have been ignored and they have been considered waste products of pregnancy. This review provides evidence for key roles of both fructose and lactate in support of key metabolic pathways required for growth and development of fetal-placental tissues, implantation and placentation. The uterus and placenta of ungulates convert glucose to fructose via the polyol pathway. Fructose is sequestered within the uterus and cannot be transported back into the maternal circulation. Fructose is phosphorylated by ketohexokinase to fructose-1-PO4 (F1P) by that is metabolized via the fructolysis pathway to yield dihydoxyacetone phosphate and glyceraldehyde-3-PO4 that are downstream of phosphofructokinase. Thus, there is no inhibition of the fructolysis pathway by low pH, citrate or ATP which allows F1P to continuously generate substrates for the pentose cycle, hexosamine biosynthesis pathway, one-carbon metabolism and tricarboxylic acid cycle, as well as lactate. Lactate sustains the activity of hypoxia-inducible factor alpha and its downstream targets such as vascular endothelial growth factor to increase utero-placental blood flow critical to growth and development of the fetal-placental tissues and a successful outcome of pregnancy. Pregnancy has been referred to as a controlled cancer and this review addresses similarities regarding metabolic aspects of tumors and the placenta.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"249 ","pages":"10200"},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617703","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