BioFactorsPub Date : 2024-01-16DOI: 10.1002/biof.2039
Toufik Abdul-Rahman, Wireko Andrew Awuah, Tatiana Mikhailova, Jacob Kalmanovich, Aashna Mehta, Jyi Cheng Ng, Megan Ariel Coghlan, Marija Zivcevska, Alexander J. Tedeschi, Emerson Costa de Oliveira, Akinchita Kumar, Emiliano Cantu-Herrera, Mykola Lyndin, Kateryna Sikora, Athanasios Alexiou, Anwar L. Bilgrami, Khalid Mohammed Al-Ghamdi, Asma Perveen, Marios Papadakis, Ghulam Md Ashraf
{"title":"Antioxidant, anti-inflammatory and epigenetic potential of curcumin in Alzheimer's disease","authors":"Toufik Abdul-Rahman, Wireko Andrew Awuah, Tatiana Mikhailova, Jacob Kalmanovich, Aashna Mehta, Jyi Cheng Ng, Megan Ariel Coghlan, Marija Zivcevska, Alexander J. Tedeschi, Emerson Costa de Oliveira, Akinchita Kumar, Emiliano Cantu-Herrera, Mykola Lyndin, Kateryna Sikora, Athanasios Alexiou, Anwar L. Bilgrami, Khalid Mohammed Al-Ghamdi, Asma Perveen, Marios Papadakis, Ghulam Md Ashraf","doi":"10.1002/biof.2039","DOIUrl":"10.1002/biof.2039","url":null,"abstract":"<p>Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin—an integral component of traditional medicine in numerous cultures worldwide—has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471873","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}
{"title":"Harnessing tumor-derived exosomes: A promising approach for the expansion of clinical diagnosis, prognosis, and therapeutic outcome of prostate cancer","authors":"Mohammad-Bagher Pirouzpanah, Soraya Babaie, Samira Pourzeinali, Hamed Valizadeh, Samira Malekeh, Fikrettin Şahin, Azizeh Farshbaf-Khalili","doi":"10.1002/biof.2036","DOIUrl":"10.1002/biof.2036","url":null,"abstract":"<p>Prostate cancer is the second leading cause of men's death worldwide. Although early diagnosis and therapy for localized prostate cancer have improved, the majority of men with metastatic disease die from prostate cancer annually. Therefore, identification of the cellular-molecular mechanisms underlying the progression of prostate cancer is essential for overcoming controlled proliferation, invasion, and metastasis. Exosomes are small extracellular vesicles that mediate most cells' interactions and contain membrane proteins, cytosolic and nuclear proteins, extracellular matrix proteins, lipids, metabolites, and nucleic acids. Exosomes play an essential role in paracrine pathways, potentially influencing Prostate cancer progression through a wide variety of mechanisms. In the present review, we outline and discuss recent progress in our understanding of the role of exosomes in the Prostate cancer microenvironment, like their involvement in prostate cancer occurrence, progression, angiogenesis, epithelial–mesenchymal transition, metastasis, and drug resistance. We also present the latest findings regarding the function of exosomes as biomarkers, direct therapeutic targets in prostate cancer, and the challenges and advantages associated with using exosomes as natural carriers and in exosome-based immunotherapy. These findings are a promising avenue for the expansion of potential clinical approaches.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416279","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}
BioFactorsPub Date : 2024-01-09DOI: 10.1002/biof.2038
Marko Miler, Jasmina Živanović, Vladimir Ajdžanović, Dragan Milenkovic, Thais Cesar, Miloš R. Filipović, Verica Milošević
{"title":"Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats","authors":"Marko Miler, Jasmina Živanović, Vladimir Ajdžanović, Dragan Milenkovic, Thais Cesar, Miloš R. Filipović, Verica Milošević","doi":"10.1002/biof.2038","DOIUrl":"10.1002/biof.2038","url":null,"abstract":"<p>Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24-month-old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for 4 weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total -SH groups and malonaldehyde; MDA), liver enzymes in serum and <i>in silico</i> analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate–cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old-aged liver.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401671","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}
BioFactorsPub Date : 2024-01-09DOI: 10.1002/biof.2037
Laura Corrales-Guerrero, Irene Díaz-Moreno
{"title":"Deciphering the role of Zn2+-binding histidines from TIA-1 on the assembly and dynamics of stress granules","authors":"Laura Corrales-Guerrero, Irene Díaz-Moreno","doi":"10.1002/biof.2037","DOIUrl":"10.1002/biof.2037","url":null,"abstract":"<p>T-cell intracellular antigen-1 (TIA-1) is a key RNA-binding protein that participates in translation regulation and RNA splicing. TIA-1 undergoes liquid–liquid phase separation as a fundamental mechanism that enables the condensation of RNA and proteins into membraneless organelles called stress granules (SGs). However, this dynamic behavior can lead to aberrant fibril formation, implicated in neurodegenerative disorders, and must be tightly regulated. In this study, we investigated the role in the cell of histidine residues His94 and His96, responsible for Zn<sup>2+</sup> binding. Using fluorescence microscopy, we found that the specific binding site formed by these residues is critical for SG assembly. Furthermore, it also plays a role maintaining the dynamic behavior of SG-assembled TIA-1. Collectively, our findings confirm the physiological relevance of TIA-1 His94 and His96 in the Zn<sup>2+</sup>-mediated regulatory mechanism for protection against fibril formation in SGs.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401670","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}
BioFactorsPub Date : 2024-01-06DOI: 10.1002/biof.2028
Malvin Ofosu-Boateng, Fathima Shaik, Sora Choi, Frederick A. Ekuban, Lidya H. Gebreyesus, Elizabeth Twum, Daniel O. Nnamani, Susan T. Yeyeodu, Nour Yadak, Daniel M. Collier, Maxwell A. Gyamfi
{"title":"High-fat diet induced obesity promotes inflammation, oxidative stress, and hepatotoxicity in female FVB/N mice","authors":"Malvin Ofosu-Boateng, Fathima Shaik, Sora Choi, Frederick A. Ekuban, Lidya H. Gebreyesus, Elizabeth Twum, Daniel O. Nnamani, Susan T. Yeyeodu, Nour Yadak, Daniel M. Collier, Maxwell A. Gyamfi","doi":"10.1002/biof.2028","DOIUrl":"10.1002/biof.2028","url":null,"abstract":"<p>Although obesity and subsequent liver injury are increasingly prevalent in women, female mouse models have generally shown resistance to high-fat diet (HFD)-induced obesity. We evaluated control and HFD-fed male and female FVB/N mice, a strain well-suited to transgenic analyses, for phenotypic, histological, and molecular markers related to control of glucose, lipids, and inflammation in serum, liver, and perigonadal white adipose tissues. Unlike many mouse models, HFD-fed FVB/N females gained more perigonadal and mesenteric fat mass and overall body weight than their male counterparts, with increased hepatic expression of lipogenic PPARγ target genes (<i>Cd36</i>, <i>Fsp27</i>, and <i>Fsp27β</i>), oxidative stress genes and protein (<i>Nqo1</i> and CYP2E1), inflammatory gene (<i>Mip-2</i>), and the pro-fibrotic gene <i>Pai-1</i>, along with increases in malondialdehyde and serum ALT levels. Further, inherent to females (independently of HFD), hepatic antioxidant heme oxygenase-1 (HMOX1, HO-1) protein levels were reduced compared to their male counterparts. In contrast, males may have been relatively protected from HFD-induced oxidative stress and liver injury by elevated mRNA and protein levels of hepatic antioxidants BHMT and <i>Gpx2</i>, increased fatty acid oxidation genes in liver and adipocytes (Pparδ), despite disorganized and inflamed adipocytes. Thus, female FVB/N mice offer a valuable preclinical, genetically malleable model that recapitulates many of the features of diet-induced obesity and liver damage observed in human females.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110742","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}
BioFactorsPub Date : 2024-01-02DOI: 10.1002/biof.2034
Maged Alkanad, Umme Hani, Annegowda H V, Mohammed Ghazwani, Nazima Haider, Riyaz Ali M. Osmani, Pandareesh M D, Hamsalakshmi, Rajeev Bhat
{"title":"Bitter yet beneficial: The dual role of dietary alkaloids in managing diabetes and enhancing cognitive function","authors":"Maged Alkanad, Umme Hani, Annegowda H V, Mohammed Ghazwani, Nazima Haider, Riyaz Ali M. Osmani, Pandareesh M D, Hamsalakshmi, Rajeev Bhat","doi":"10.1002/biof.2034","DOIUrl":"10.1002/biof.2034","url":null,"abstract":"<p>With the rising prevalence of diabetes and its association with cognitive impairment, interest in the use of dietary alkaloids and other natural products has grown significantly. Understanding how these compounds manage diabetic cognitive dysfunction (DCD) is crucial. This comprehensive review explores the etiology of DCD and the effects of alkaloids in foods and dietary supplements that have been investigated as DCD therapies. Data on how dietary alkaloids like berberine, trigonelline, caffeine, capsaicin, 1-deoxynojirimycin, nuciferine, neferine, aegeline, tetramethylpyrazine, piperine, and others regulate cognition in diabetic disorders were collected from PubMed, Research Gate, Web of Science, Science Direct, and other relevant databases. Dietary alkaloids could improve memory in behavioral models and modulate the mechanisms underlying the cognitive benefits of these compounds, including their effects on glucose metabolism, gut microbiota, vasculopathy, neuroinflammation, and oxidative stress. Evidence suggests that dietary alkaloids hold promise for improving cognition in diabetic patients and could open exciting avenues for future research in diabetes management.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085728","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":"Integration of miRNA in exosomes and single-cell RNA-seq profiles in endemic osteoarthritis, Kashin–Beck disease","authors":"Xi Wang, Yu Zhang, Yifan Wu, Chaowei Wang, Shujin Li, Yuequan Yuan, Xi Lv, Yanli Liu, Feihong Chen, Sijie Chen, Feiyu Zhang, Xiong Guo, Yujie Ning, Hongmou Zhao","doi":"10.1002/biof.2033","DOIUrl":"10.1002/biof.2033","url":null,"abstract":"<p>Kashin–Beck disease (KBD) is an endemic, chronic degenerative joint disease in China. Exosomes miRNAs, as signaling molecules in intercellular communication, can transfer specific biological martials into target cell to regulate their function and might participate in the pathogenesis of KBD. We isolated serum and chondrocytes-derived exosomes, miRNA sequencing revealed exosomes miRNA profiles and differentially expressed miRNAs (DE-miRNAs) were identified. The target genes were predicted of known and novel DE-miRNAs with TargetScan 5.0 and miRanda 3.3a database. Single-cell RNA sequencing (scRNA-seq) was performed to identify chondrocyte clusters and their gene signatures in KBD. And we performed comparative analysis between the serum and chondrocytes-derived exosomes DE-miRNA target genes and differentially expressed genes of each cell clusters. A total of 20 DE-miRNAs were identified in serum-derived exosomes. In the miRNA expression of chondrocytes-derived exosomes, 53 DE-miRNAs were identified. 16,063 predicted targets were identified as the target genes in the serum-derived exosomes, 57,316 predicted targets were identified as the target genes in the chondrocytes-derived exosomes. Seven clusters were labeled by cell type according to the expression of previously described markers. Three hundred fifteen common genes were found among serum/chondrocytes-derived exosomes DE-miRNA target genes and DEGs identified by scRNA-seq analysis. We firstly integratly analyzed the serum and chondrocytes exosomes miRNA with single-cell RNA sequencing (scRNA-seq) data of KBD chondrocyte, the results showed that DE-miRNAs in exosomes might play a potential role in regulating genes expression in different KBD chondrocytes clusters by exosomes mediating cell–cell communications functions, which could improve the new diagnosis and treatment methods for KBD.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139068876","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}
BioFactorsPub Date : 2023-12-29DOI: 10.1002/biof.2032
Huilin Deng, Xinrui Rao, Sijia Zhang, Leichong Chen, Yan Zong, Rui Zhou, Rui Meng, Xiaorong Dong, Gang Wu, Qianwen Li
{"title":"Protein kinase CK2: An emerging regulator of cellular metabolism","authors":"Huilin Deng, Xinrui Rao, Sijia Zhang, Leichong Chen, Yan Zong, Rui Zhou, Rui Meng, Xiaorong Dong, Gang Wu, Qianwen Li","doi":"10.1002/biof.2032","DOIUrl":"10.1002/biof.2032","url":null,"abstract":"<p>The protein kinase casein kinase 2 (CK2) exerts its influence on the metabolism of three major cellular substances by phosphorylating essential protein molecules involved in various cellular metabolic pathways. These substances include hormones, especially insulin, rate-limiting enzymes, transcription factors of key genes, and cytokines. This regulatory role of CK2 is closely tied to important cellular processes such as cell proliferation and apoptosis. Additionally, tumor cells undergo metabolic reprogramming characterized by aerobic glycolysis, accelerated lipid β-oxidation, and abnormally active glutamine metabolism. In this context, CK2, which is overexpressed in various tumors, also plays a pivotal role. Hence, this review aims to summarize the regulatory mechanisms of CK2 in diverse metabolic pathways and tumor development, providing novel insights for the diagnosis, treatment, and prognosis of metabolism-related diseases and cancers.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139068869","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}
BioFactorsPub Date : 2023-12-27DOI: 10.1002/biof.2031
Zizhang Guo, Yeqing Tang, Shunshun Wang, Yuming Huang, Qingjia Chi, Kang Xu, Lei Xue
{"title":"Natural product fargesin interferes with H3 histone lactylation via targeting PKM2 to inhibit non-small cell lung cancer tumorigenesis","authors":"Zizhang Guo, Yeqing Tang, Shunshun Wang, Yuming Huang, Qingjia Chi, Kang Xu, Lei Xue","doi":"10.1002/biof.2031","DOIUrl":"10.1002/biof.2031","url":null,"abstract":"<p>Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. There is an urgent need to find more effective drugs that inhibit NSCLC. Fargesin (FGS) has demonstrated anti-tumor effects; however, its efficacy and the molecular mechanism of inhibiting NSCLC are unclear. Herein, we investigated FGS’ inhibitory effects on NSCLC by CCK8 and EdU assays and cell cycle analysis of A549 cells in vitro and in a nude mouse tumor transplantation model in vivo. FGS (10–50 μM) significantly inhibited cell proliferation and down-regulated expression levels of <i>CDK1</i> and <i>CCND1</i>. Transcriptomic analysis showed that FGS regulated the cell metabolic process pathway. Differential metabolites with FGS treatment were enriched in glycolysis and pyruvate pathways. Cell metabolism assay were used to evaluate the oxygen consumption rate (OCR), Extracellular acidification rate (ECAR) in A549 cells. FGS also inhibited the production of cellular lactate and the expression of LDHA, LDHB, PKM2, and SLC2A1. These genes were identified as important oncogenes in lung cancer, and their binding to FGS was confirmed by molecular docking simulation. Notably, the over-expression and gene silencing experiments signified PKM2 as the molecular target of FGS for anti-tumorigenesis. Moreover, the H3 histone lactylation, were correlated with tumorigenesis, were inhibited with FGS treatment. Conclusively, FGS inhibited the aerobic glycolytic and H3 histone lactylation signaling pathways in A549 NSCLC cells by targeting PKM2. These findings provide evidence of the therapeutic potential of FGS in NSCLC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039465","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}
BioFactorsPub Date : 2023-12-27DOI: 10.1002/biof.2030
Catarina S. Lopes, Ana Catarina Pronto-Laborinho, Vasco A. Conceição, Teresa Freitas, Gonçalo L. Matias, Marta Gromicho, Nuno C. Santos, Mamede de Carvalho, Filomena A. Carvalho
{"title":"Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients","authors":"Catarina S. Lopes, Ana Catarina Pronto-Laborinho, Vasco A. Conceição, Teresa Freitas, Gonçalo L. Matias, Marta Gromicho, Nuno C. Santos, Mamede de Carvalho, Filomena A. Carvalho","doi":"10.1002/biof.2030","DOIUrl":"10.1002/biof.2030","url":null,"abstract":"<p>Erythrocytes play a fundamental role in oxygen delivery to tissues and binding to inflammatory mediators. Evidences suggest that dysregulated erythrocyte function could contribute to the pathophysiology of several neurodegenerative diseases. We aimed to evaluate changes in morphological, biomechanical, and biophysical properties of erythrocytes from amyotrophic lateral sclerosis (ALS) patients, as new areas of study in this disease. Blood samples were collected from ALS patients, comparing with healthy volunteers. Erythrocytes were assessed using atomic force microscopy (AFM) and zeta potential analysis. The patients' motor and respiratory functions were evaluated using the revised ALS Functional Rating Scale (ALSFRS-R) and percentage of forced vital capacity (%FVC). Patient survival was also assessed. Erythrocyte surface roughness was significantly smoother in ALS patients, and this parameter was a predictor of faster decline in ALSFRS-R scores. ALS patients exhibited higher erythrocyte stiffness, as indicated by reduced AFM tip penetration depth, which predicted a faster ALSFRS-R score and respiratory subscore decay. A lower negative charge on the erythrocyte membrane was predictor of a faster ALSFRS-R and FVC decline. Additionally, a larger erythrocyte surface area was an independent predictor of lower survival. These changes in morphological and biophysical membrane properties of ALS patients' erythrocytes, lead to increased cell stiffness and morphological variations. We speculate that these changes might precipitate motoneurons dysfunction and accelerate disease progression. Further studies should explore the molecular alterations related to these observations. Our findings may contribute to dissect the complex interplay between respiratory function, tissue hypoxia, progression rate, and survival in ALS.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039464","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}