Biomolecules最新文献_第9页

Connecting the Dots: Telomere Shortening and Rheumatic Diseases. 连接点：端粒缩短与风湿病。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-06 DOI: 10.3390/biom14101261

Fang Han, Farooq Riaz, Jincheng Pu, Ronglin Gao, Lufei Yang, Yanqing Wang, Jiamin Song, Yuanyuan Liang, Zhenzhen Wu, Chunrui Li, Jianping Tang, Xianghuai Xu, Xuan Wang

{"title":"Connecting the Dots: Telomere Shortening and Rheumatic Diseases.","authors":"Fang Han, Farooq Riaz, Jincheng Pu, Ronglin Gao, Lufei Yang, Yanqing Wang, Jiamin Song, Yuanyuan Liang, Zhenzhen Wu, Chunrui Li, Jianping Tang, Xianghuai Xu, Xuan Wang","doi":"10.3390/biom14101261","DOIUrl":"https://doi.org/10.3390/biom14101261","url":null,"abstract":"Telomeres, repetitive sequences located at the extremities of chromosomes, play a pivotal role in sustaining chromosomal stability. Telomerase is a complex enzyme that can elongate telomeres by appending telomeric repeats to chromosome ends and acts as a critical factor in telomere dynamics. The gradual shortening of telomeres over time is a hallmark of cellular senescence and cellular death. Notably, telomere shortening appears to result from the complex interplay of two primary mechanisms: telomere shelterin complexes and telomerase activity. The intricate interplay of genetic, environmental, and lifestyle influences can perturb telomere replication, incite oxidative stress damage, and modulate telomerase activity, collectively resulting in shifts in telomere length. This age-related process of telomere shortening plays a considerable role in various chronic inflammatory and oxidative stress conditions, including cancer, cardiovascular disease, and rheumatic disease. Existing evidence has shown that abnormal telomere shortening or telomerase activity abnormalities are present in the pathophysiological processes of most rheumatic diseases, including different disease stages and cell types. The impact of telomere shortening on rheumatic diseases is multifaceted. This review summarizes the current understanding of the link between telomere length and rheumatic diseases in clinical patients and examines probable telomere shortening in peripheral blood mononuclear cells and histiocytes. Therefore, understanding the intricate interaction between telomere shortening and various rheumatic diseases will help in designing personalized treatment and control measures for rheumatic disease.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

MicroRNA-503 Suppresses Oral Mucosal Fibroblast Differentiation by Regulating RAS/RAF/MEK/ERK Signaling Pathway. MicroRNA-503 通过调节 RAS/RAF/MEK/ERK 信号通路抑制口腔黏膜成纤维细胞分化

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-05 DOI: 10.3390/biom14101259

Dada Wen, Huamin Zhang, Yutong Zhou, Ni Jian, Canhua Jiang, Jie Wang

{"title":"MicroRNA-503 Suppresses Oral Mucosal Fibroblast Differentiation by Regulating RAS/RAF/MEK/ERK Signaling Pathway.","authors":"Dada Wen, Huamin Zhang, Yutong Zhou, Ni Jian, Canhua Jiang, Jie Wang","doi":"10.3390/biom14101259","DOIUrl":"https://doi.org/10.3390/biom14101259","url":null,"abstract":"The abnormal proliferation and differentiation of oral mucosal fibroblasts (FBs) is the key to the progression of oral submucosal fibrosis. To clarify the mechanism of platelet-derived growth factor (PDGF-BB)-induced FBs fibrosis in oral mucosa, real-time quantitative polymerase chain reaction and Western blot were used in this study to detect the expression of miR-503 and the expression of p-MEK, p-ERK, miR-503, RAF, smooth actin and type I collagen under different time and concentration stimulation of PDGF-BB. The effects of overexpression of miR-503 or RAF on the proliferation and migration of FBs were detected by cell counting kit 8 and cell scratch assay, respectively. A dual luciferase reporter gene assay was used to verify the targeting effect of miR-503 on RAF. The results showed that miR-503 was downregulated in a dose- and time-dependent manner in PDGF-BB-induced FBs. In addition, RAF is a direct target of miR-503 and can be negatively regulated. Overexpression of RAF can promote FB proliferation, migration, differentiation, collagen synthesis, and activation of downstream molecules (MEK/ERK), while overexpression of miR-503 can partially reverse the effects of RAF. Therefore, miR-503 regulates the biological behavior of PDGF-BB-induced oral mucosal FBs by influencing the activation of the RAS/RAF/MEK/ERK signaling pathway.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

EMC1 Is Required for the Sarcoplasmic Reticulum and Mitochondrial Functions in the Drosophila Muscle. 果蝇肌肉中的肉质网和线粒体功能离不开 EMC1

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-05 DOI: 10.3390/biom14101258

Carlos Antonio Couto-Lima, Maiaro Cabral Rosa Machado, Lucas Anhezini, Marcos Túlio Oliveira, Roberto Augusto da Silva Molina, Rodrigo Ribeiro da Silva, Gabriel Sarti Lopes, Vitor Trinca, David Fernando Colón, Pablo M Peixoto, Nadia Monesi, Luciane Carla Alberici, Ricardo Guelerman P Ramos, Enilza Maria Espreafico

{"title":"EMC1 Is Required for the Sarcoplasmic Reticulum and Mitochondrial Functions in the Drosophila Muscle.","authors":"Carlos Antonio Couto-Lima, Maiaro Cabral Rosa Machado, Lucas Anhezini, Marcos Túlio Oliveira, Roberto Augusto da Silva Molina, Rodrigo Ribeiro da Silva, Gabriel Sarti Lopes, Vitor Trinca, David Fernando Colón, Pablo M Peixoto, Nadia Monesi, Luciane Carla Alberici, Ricardo Guelerman P Ramos, Enilza Maria Espreafico","doi":"10.3390/biom14101258","DOIUrl":"https://doi.org/10.3390/biom14101258","url":null,"abstract":"EMC1 is part of the endoplasmic reticulum (ER) membrane protein complex, whose functions include the insertion of transmembrane proteins into the ER membrane, ER-mitochondria contact, and lipid exchange. Here, we show that the Drosophila melanogaster EMC1 gene is expressed in the somatic musculature and the protein localizes to the sarcoplasmic reticulum (SR) network. Muscle-specific EMC1 RNAi led to severe motility defects and partial late pupae/early adulthood lethality, phenotypes that are rescued by co-expression with an EMC1 transgene. Motility impairment in EMC1-depleted flies was associated with aberrations in muscle morphology in embryos, larvae, and adults, including tortuous and misaligned fibers with reduced size and weakness. They were also associated with an altered SR network, cytosolic calcium overload, and mitochondrial dysfunction and dysmorphology that impaired membrane potential and oxidative phosphorylation capacity. Genes coding for ER stress sensors, mitochondrial biogenesis/dynamics, and other EMC components showed altered expression and were mostly rescued by the EMC1 transgene expression. In conclusion, EMC1 is required for the SR network's mitochondrial integrity and influences underlying programs involved in the regulation of muscle mass and shape. We believe our data can contribute to the biology of human diseases caused by EMC1 mutations.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Advancing Roles and Therapeutic Potentials of Pyroptosis in Host Immune Defenses against Tuberculosis. 促进宿主对结核病的免疫防御中热蛋白沉积的作用和治疗潜力。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-04 DOI: 10.3390/biom14101255

Jiayi Yang, Yuhe Ma, Jiaqi Yu, Yilin Liu, Jiaojiao Xia, Xinen Kong, Xiaoying Jin, Jiaxiang Li, Siqi Lin, Yongdui Ruan, Fen Yang, Jiang Pi

{"title":"Advancing Roles and Therapeutic Potentials of Pyroptosis in Host Immune Defenses against Tuberculosis.","authors":"Jiayi Yang, Yuhe Ma, Jiaqi Yu, Yilin Liu, Jiaojiao Xia, Xinen Kong, Xiaoying Jin, Jiaxiang Li, Siqi Lin, Yongdui Ruan, Fen Yang, Jiang Pi","doi":"10.3390/biom14101255","DOIUrl":"https://doi.org/10.3390/biom14101255","url":null,"abstract":"Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, remains a deadly global public health burden. The use of recommended drug combinations in clinic has seen an increasing prevalence of drug-resistant TB, adding to the impediments to global control of TB. Therefore, control of TB and drug-resistant TB has become one of the most pressing issues in global public health, which urges the exploration of potential therapeutic targets in TB and drug-resistant TB. Pyroptosis, a form of programmed cell death characterized by cell swelling and rupture, release of cellular contents and inflammatory responses, has been found to promote pathogen clearance and adopt crucial roles in the control of bacterial infections. It has been demonstrated that Mtb can cause host cell pyroptosis, and these host cells, which are infected by Mtb, can kill Mtb accompanied by pyroptosis, while, at the same time, pyroptosis can also release intracellular Mtb, which may potentially worsen the infection by exacerbating the inflammation. Here, we describe the main pathways of pyroptosis during Mtb infection and summarize the identified effectors of Mtb that regulate pyroptosis to achieve immune evasion. Moreover, we also discuss the potentials of pyroptosis to serve as an anti-TB therapeutic target, with the aim of providing new ideas for the development of TB treatments.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation. 化合物 K 通过激活 NLRP3 炎症小体促进巨核细胞分化

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-04 DOI: 10.3390/biom14101257

Seonhwa Hwang, Min-Seo Park, Anthony Junhoe Koo, Eunsoo Yoo, Seh-Hyon Song, Hye-Kyung Kim, Min-Hi Park, Jae-Seon Kang

{"title":"Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation.","authors":"Seonhwa Hwang, Min-Seo Park, Anthony Junhoe Koo, Eunsoo Yoo, Seh-Hyon Song, Hye-Kyung Kim, Min-Hi Park, Jae-Seon Kang","doi":"10.3390/biom14101257","DOIUrl":"https://doi.org/10.3390/biom14101257","url":null,"abstract":"Platelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer's disease. Enhancing megakaryocytic differentiation is a promising strategy to increase platelet production. Compound K (CK), a major bioactive metabolite of ginsenosides from Panax ginseng, has demonstrated anti-cancer and neuroprotective properties. In this study, we investigated the effects of CK on megakaryocytic differentiation and apoptosis in chronic myeloid leukemia (CML) cell lines K562 and Meg-01. CK treatment significantly upregulated the mRNA expression of key megakaryocytic differentiation markers, including CD61, CD41, and CD42a, and promoted the formation of large, multinucleated cells in K562 cells. Additionally, flow cytometry analysis revealed that CK at 5 µM induced apoptosis, a critical process in thrombocytopoiesis, in both K562 and Meg-01 cells. RT2 Profiler PCR array analysis further identified a marked increase in the expression of genes associated with the activation of the NLRP3 inflammasome in CK-treated K562 and Meg-01 cells. This study is the first to demonstrate that CK promotes megakaryocytic differentiation and apoptosis through the activation of the ERK/EGR1 and NLRP3 inflammasome pathways. These findings suggest that CK may enhance platelet production, indicating its potential as a therapeutic candidate for platelet-related disorders and other associated diseases.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Necrotizing Enterocolitis and Neurodevelopmental Impairments: Microbiome, Gut, and Brain Entanglements. 坏死性小肠结肠炎与神经发育障碍：微生物组、肠道和大脑的纠葛。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-04 DOI: 10.3390/biom14101254

Cuilee Sha, Zhaosheng Jin, Stella Y Ku, Ann S Kogosov, Sun Yu, Sergio D Bergese, Helen Hsieh

{"title":"Necrotizing Enterocolitis and Neurodevelopmental Impairments: Microbiome, Gut, and Brain Entanglements.","authors":"Cuilee Sha, Zhaosheng Jin, Stella Y Ku, Ann S Kogosov, Sun Yu, Sergio D Bergese, Helen Hsieh","doi":"10.3390/biom14101254","DOIUrl":"https://doi.org/10.3390/biom14101254","url":null,"abstract":"There is significant communication and interdependence among the gut, the microbiome, and the brain during development. Diseases, such as necrotizing enterocolitis (NEC), highlight how injury to the immature gastrointestinal tract leads to long-term neurological consequences, due to vulnerabilities of the brain in the early stages of life. A better understanding of the developing gut-microbiota-brain axis is needed to both prevent and treat the devastating consequences of these disease processes. The gut-microbiota-brain axis is a bidirectional communication pathway that includes metabolic, nervous, endocrine, and immune components. In this review, we discuss gut development, microbiome colonization and maturation, and the interactions that influence neurodevelopment in the context of NEC. We describe the components of the gut-brain axis and how the microbiome is an integral member of this relationship. Finally, we explore how derangements within the microbiome and gut-microbiota-brain axis affect the normal development and function of the other systems and long-term neurodevelopmental consequences for patients.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Cellular Profile of Subfornical Organ Insulin Receptors in Mice. 小鼠角膜下器官胰岛素受体的细胞特征

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-04 DOI: 10.3390/biom14101256

Han-Rae Kim, Jin-Kwon Jeong, Colin N Young

{"title":"Cellular Profile of Subfornical Organ Insulin Receptors in Mice.","authors":"Han-Rae Kim, Jin-Kwon Jeong, Colin N Young","doi":"10.3390/biom14101256","DOIUrl":"https://doi.org/10.3390/biom14101256","url":null,"abstract":"Brain insulin receptor signaling is strongly implicated in cardiovascular and metabolic physiological regulation. In particular, we recently demonstrated that insulin receptors within the subfornical organ (SFO) play a tonic role in cardiovascular and metabolic regulation in mice. The SFO is a forebrain sensory circumventricular organ that regulates cardiometabolic homeostasis due to its direct exposure to the circulation and thus its ability to sense circulating factors, such as insulin. Previous work has demonstrated broad distribution of insulin receptor-expressing cells throughout the entire SFO, indirectly indicating insulin receptor expression in multiple cell types. Based on this, we sought to determine the cellular phenotypes that express insulin receptors within the SFO by combining immunohistochemistry with genetically modified reporter mouse models. Interestingly, SFO neurons, including both excitatory and inhibitory types, were the dominant cell site for insulin receptor expression, although a weak degree of insulin receptor expression was also detected in astrocytes. Moreover, SFO angiotensin type 1a receptor neurons also expressed insulin receptors. Collectively, these anatomical findings indicate the existence of potentially complex cellular networks within the SFO through which insulin signaling can influence physiology and further point to the SFO as a possible brain site for crosstalk between angiotensin-II and insulin.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Investigation of the Roles of Phosphatidylinositol 4-Phosphate 5-Kinases 7,9 and Wall-Associated Kinases 1-3 in Responses to Indole-3-Carbinol and Biotic Stress in Arabidopsis Thaliana. 拟南芥中磷脂酰肌醇 4-磷酸 5-激酶 7、9 和壁相关激酶 1-3 对吲哚-3-卡比醇和生物胁迫反应的作用研究

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-03 DOI: 10.3390/biom14101253

Hala Khamesa-Israelov, Alin Finkelstein, Eilon Shani, Daniel A Chamovitz

{"title":"Investigation of the Roles of Phosphatidylinositol 4-Phosphate 5-Kinases 7,9 and Wall-Associated Kinases 1-3 in Responses to Indole-3-Carbinol and Biotic Stress in Arabidopsis Thaliana.","authors":"Hala Khamesa-Israelov, Alin Finkelstein, Eilon Shani, Daniel A Chamovitz","doi":"10.3390/biom14101253","DOIUrl":"https://doi.org/10.3390/biom14101253","url":null,"abstract":"Indole-3-carbinol (I3C), a hydrolysis product of indole-3-methylglucosinolate, is toxic to herbivorous insects and pathogens. In mammals, I3C is extensively studied for its properties in cancer prevention and treatment. Produced in Brassicaceae, I3C reversibly inhibits root elongation in a concentration-dependent manner. This inhibition is partially explained by the antagonistic action of I3C on auxin signaling through TIR1. To further elucidate the mode of action of I3C in plants, we have employed a forward-genetic amiRNA screen that circumvents functional redundancy. We identified and characterized two amiRNA lines with impaired I3C response. The first line, ICT2, targets the phosphatidylinositol 4-phosphate 5-kinase family (PIP5K), exhibiting tolerance to I3C, while the second line, ICS1, targets the Wall-Associated Kinases (WAK1-3) family, showing susceptibility to I3C. Both lines maintain I3C-induced antagonism of auxin signaling, indicating that their phenotypes are due to auxin-independent mechanisms. Transcript profiling experiments reveal that both lines are transcriptionally primed to respond to I3C treatment. Physiological, metabolomic, and transcriptomic analysis reveal that these kinases mediate numerous developmental processes and are involved in abiotic and biotic stress responses.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Design of a Robust Flow Cytometric Approach for Phenotypical and Functional Analysis of Human Monocyte Subsets in Health and Disease. 设计一种可靠的流式细胞仪方法，用于对健康和疾病中的人类单核细胞亚群进行表型和功能分析。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-03 DOI: 10.3390/biom14101251

Talia Ahrazoglu, Jennifer Isabel Kluczny, Patricia Kleimann, Lisa-Marie Irschfeld, Fabian Theodor Nienhaus, Florian Bönner, Norbert Gerdes, Sebastian Temme

{"title":"Design of a Robust Flow Cytometric Approach for Phenotypical and Functional Analysis of Human Monocyte Subsets in Health and Disease.","authors":"Talia Ahrazoglu, Jennifer Isabel Kluczny, Patricia Kleimann, Lisa-Marie Irschfeld, Fabian Theodor Nienhaus, Florian Bönner, Norbert Gerdes, Sebastian Temme","doi":"10.3390/biom14101251","DOIUrl":"https://doi.org/10.3390/biom14101251","url":null,"abstract":"Human monocytes can be subdivided into phenotypically and functionally different classical, intermediate and non-classical monocytes according to the cell surface expression of CD14 and CD16. A precise identification and characterisation of monocyte subsets is necessary to unravel their role in inflammatory diseases. Here, we compared three different flow cytometric strategies (A-C) and found that strategy C, which included staining against CD11b, HLA-DR, CD14 and CD16, followed by several gating steps, most reliably identified monocyte subtypes in blood samples from healthy volunteers and from patients with stable coronary heart disease (CHD) or ST-elevation myocardial infarction (STEMI). Additionally, we established a fixation and permeabilisation protocol to enable the analysis of intracellular markers. We investigated the phagocytosis of lipid nanoparticles, the uptake of 2-NBD-glucose and the intracellular levels of CD74 and HLA-DM. This revealed that classical and intermediate monocytes from patients with STEMI showed the highest uptake of 2-NBD-glucose, whereas classical and intermediate monocytes from patients with CHD took up the largest amounts of lipid nanoparticles. Interestingly, intermediate monocytes had the highest expression level of HLA-DM. Taken together, we present a robust flow cytometric approach for the identification and functional characterisation of monocyte subtypes in healthy humans and patients with diseases.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Deficiency in Glutamine-Fructose-6-Phosphate Transaminase 1 (Gfpt1) in Skeletal Muscle Results in Reduced Glycosylation of the Delta Subunit of the Nicotinic Acetylcholine Receptor (AChRδ). 骨骼肌中谷氨酰胺-果糖-6-磷酸转氨酶 1 (Gfpt1) 的缺陷导致烟碱乙酰胆碱受体 (AChRδ) δ 亚基的糖基化减少

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-03 DOI: 10.3390/biom14101252

Stephen Henry Holland, Ricardo Carmona-Martinez, Kaela O'Connor, Daniel O'Neil, Andreas Roos, Sally Spendiff, Hanns Lochmüller

{"title":"A Deficiency in Glutamine-Fructose-6-Phosphate Transaminase 1 (Gfpt1) in Skeletal Muscle Results in Reduced Glycosylation of the Delta Subunit of the Nicotinic Acetylcholine Receptor (AChRδ).","authors":"Stephen Henry Holland, Ricardo Carmona-Martinez, Kaela O'Connor, Daniel O'Neil, Andreas Roos, Sally Spendiff, Hanns Lochmüller","doi":"10.3390/biom14101252","DOIUrl":"https://doi.org/10.3390/biom14101252","url":null,"abstract":"The neuromuscular junction (NMJ) is the site where the motor neuron innervates skeletal muscle, enabling muscular contraction. Congenital myasthenic syndromes (CMS) arise when mutations in any of the approximately 35 known causative genes cause impaired neuromuscular transmission at the NMJ, resulting in fatigable muscle weakness. A subset of five of these CMS-causative genes are associated with protein glycosylation. Glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) is the rate-limiting enzyme within the hexosamine biosynthetic pathway (HBP), a metabolic pathway that produces the precursors for glycosylation. We hypothesized that deficiency in Gfpt1 expression results in aberrant or reduced glycosylation, impairing the proper assembly and stability of key NMJ-associated proteins. Using both in vitro and in vivo Gfpt1-deficient models, we determined that the acetylcholine receptor delta subunit (AChRδ) has reduced expression and is hypo-glycosylated. Using laser capture microdissection, NMJs were harvested from Gfpt1 knockout mouse muscle. A lower-molecular-weight species of AChRδ was identified at the NMJ that was not detected in controls. Furthermore, Gfpt1-deficient muscle lysates showed impairment in protein O-GlcNAcylation and sialylation, suggesting that multiple glycan chains are impacted. Other key NMJ-associated proteins, in addition to AChRδ, may also be differentially glycosylated in Gfpt1-deficient muscle.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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